HX641 29950 
RC648  ,C88  1918    Thyroid  and  thymus, 


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Columbia  (Hntoettfitp 
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College  of  ^fjpstriantf  ano  burgeons 

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THYROID  AND  THYMUS 


BY 
ANDRE  CROTTI,  M.D.,  F.A.C.S.,  LL.D. 

FORMERLY  PROFESSOR  OF  CLINICAL  SURGERY  AND  ASSOCIATE  PROFESSOR  OF  ANATOMY  AT    OHIO    STATE 

UNIVERSITY  COLLEGE  OF  MEDICINE;  MEMBER  OF  THE  AMERICAN  MEDICAL  ASSOCIATION,  OHIO  STATE 

MEDICAL  ASSOCIATION,  COLUMBUS    ACADEMY  OF  MEDICINE,  AMERICAN  ASSOCIATION  OF 

OBSTETRICIANS  AND    GYNECOLOGISTS,  SOCIETY    FOR  THE  STUDY  OF  INTERNAL 

SECRETIONS,  HONORARY  MEMBER  OF  THE    WEST    VIRGINIA    STATE 

MEDICAL  SOCIETY,  SURGEON  TO  GRANT  AND  CHILDREN'S 

HOSPITALS,  COLUMBUS,    OHIO 


WITH   96   ILLUSTRATIONS  AND   33   PLATES   IN   COLORS 


LEA   &    FEBIGER 

I'll  I  LA  DEL  I'll  I  A    A.N  I)    N  IW    Y<>  K  K 


Copyright 

LEA  &   FEBIGER 

1918 


TO   THE   ONES   TO   WHOM   I   OWE   THE   MOST 

TO   MY  MOTHER 

TO  MY  WIFE 

TO   MY   LATE   CHIEF  AND   FRIEND 
PROFESSOR   HENRY   STILLING 

PROFESSOR   OF    PATHOLOGY   IN   THE   UNIVERSITY   OF   LAUSANNE,    SWITZERLAND 

TO   MY   LATE  CHIEF 
PROFESSOR   THEODORE   KOCHER 

BERNE,   SWITZERLAND 

THE   FATHER   OF   GOITER   SURGERY 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/thyroidthymusOOcrot 


PREFACE. 


The  following  pages  are  the  results  of  seventeen  years'  experience 
in  the  field  of  goiter  pathology  and  surgery  in  Switzerland  and  in 
this  country.  When  first  assistant  in  the  pathological  laboratory  of 
Prof.  Henry  Stilling,  in  Lausanne,  Switzerland,  I  felt  a  marked  attrac- 
tion toward  the  goiter  problem.  Since  then  that  interest  has  been 
steadily  growing  keener.  It  is  not  only  of  the  utmost  interest  medi- 
cally and  surgically,  but  is  also  one  of  the  most  baffling  problems  so  far 
as  the  etiology  is  concerned,  and,  furthermore,  is  of  tremendous  impor- 
tance sociologically.  The  enormous  loss  to  a  community,  to  a  state, 
to  a  country  caused  by  the  goiter  pathology,  be  it  hypothyroidism, 
hyperthyroidism,  or  cretinism,  can  scarcely  be  estimated.  Consequently 
any  effort  to  understand,  to  explain,  or  to  combat  that  ailment  should 
be  welcome.  It  was  with  this  end  in  view  that  I  started  to  write  this 
book.  Some  may  find  my  statements  somewhat  dogmatic  at  times, 
and  my  conclusions  perhaps  a  little  sanguine.  I  feel,  however,  that 
in  the  study  of  the  problems  of  internal  secretion,  always  tantalizing 
and  interesting,  accessibility  to  ideas  is  the  one  prerequisite  to  success 
for  those  who  wish  to  gain  achievement  in  the  study,  and  so  long  as  we 
have  not  acquired  the  whole  truth,  opinions  are  of  value  provided  the) 
are  substantiated  by  facts. 

In  addition  to  the  years  of  personal  experience  in  the  study  of  the 
thyroid  and  thymus  glands,  I  have  gathered  all  that  I  considered  of 
value  from  the  enormous  amount  of  French,  Italian,  German,  and 
English  literature  on  the  subject,  and  I  have  endeavored,  in  my  recital 
of  sources  and  authorities,  to  give  credit  where  credit  is  due. 

It  is  my  pleasant  duty  to  express  my  profound  gratitude  and  respect 
to  the  memory  of  my  master,  Henry  Stilling,  Professor  ol  Pathology 
at  the  University  of  Lausanne,  Switzerland.  I  <>  him  I  owe  much 
encouragement  and  self-confidence. 

1  have  hoped  that  my  great  master.  Professor  Theodore  Kocher,  of 
Berne,  Switzerland,  would  live  to  see  this  work  in  which  he  was  greatly 
interested.  Unfortunately,  it  was  not  to  be.  I  owe  so  much  to  his 
inspiration  and  example  that  his  memory  will  always  be  cherished 
by  me. 


vi  PREFACE 

It  is  with  pleasure  and  pride  that  I  acknowledge  the  invaluable 
assistance  of  my  dear  wife  in  writing  the  chapter  on  the  Etiology  of 
Simple  Goiter. 

I  wish  to  thank,  also,  Marcel  Guelin,  who  formerly  lived  in  Moscow, 
Russia,  but  is  now  "somewhere  in  Siberia.''  His  anatomical  drawings 
are  the  most  beautiful  and  artistic  I  have  ever  seen.  The  difficulty 
of  getting  these  plates  to  America  (several  sets  were  lost  on  the  way) 
was  a  bit  of  exasperation  that  was  an  expected,  though  unwelcome, 
outcome  of  the  disturbed  conditions  due  to  the  Great  War.  If  the 
work  merits  success,  my  friend  Guelin  must  be  entitled  to  a  share 
of  the  credit. 

To  J.  Philip  Schneider,  Ph.D.,  Professor  of  English,  Wittenberg 
College,  Springfield,  Ohio,  and  to  his  wife,  Clara  Serviss  Schneider,  go 
hearty  thanks  for  help  in  proof-reading,  in  seeing  the  work  through 
the  press,  and  for  the  index. 

Finally,  I  wish  to  acknowledge  the  assistance  I  have  received  from 
my  secretary,  Miss  Mary  Scully,  whose  untiring  efforts  have  been  of 
great   value. 

To  those  of  my  masters  who  are  still  alive  to  receive  this  contri- 
bution, I  send  greetings  and  offer  heartfelt  thanks  for  encouragement 
and  inspiration.  May  they  feel  that  what  of  ambition  was  aroused 
by  their  efforts  was  not  aroused  in  vain. 

I  cannot  close  the  chapter  of  my  debts  without  mentioning  Dr.  J. 
F.  Baldwin,  surgeon  at  Grant  Hospital,  Columbus,  Ohio,  and  without 
thanking  him  heartily  for  his  cordial  support  and  encouragement. 

A.  C. 

Columbus,  Ohio. 


CONTENTS. 


CHAPTER  I. 


Diseases  of  the  Thyroid  and  Thymus. 

Anatomy 17 

Blood  Supply 19 

Lymphatics        .  20 

Histology 21 

Colloid 22 

Desquamation 23 

Embryology   . 23 

Postbranchial  Bodies 27 

1  umors  of  Mesobranchial  Origin 28 

Tumors  of  Branchial  Origin 28 


CHAPTER   II. 

Physiology  of  the  Thyroid. 

History 30 

Results  of  Experimental   I  hyroidectomy         ...  31 

I  hyroid  and  Parathyroids 32 

Postoperative   letany  in  Animals ;: 

Action  of  Thyroid  Administration  and  Thyroidectomy  on  Metabolism      ...  36 

Action  of  the  Thyroid  on  the  Cardiovascular  System }J 

Action  on  the  Blood 38 

Action  on  the  Nutrition 39 

Action  on  the  Osseous  System 40 

Action  on  the  Nervous  System 40 

Modification  of  the  Urine 40 

How  Much  of  the  1  hyroid  is  it  Necessary  to  Leave  in  Order  to  Prevenl  Symptoms 

of  Thyroid  Insufficiency? 41 


CHAPTER    III. 

BlOLOGK  \l.   Cm  MISTRY. 

Iodm  in  Thyroid  (Hand 44 

Conclusions  Conc<  rning  the  I  hyroid  Function  and  Its  Chemistr}  =;i 

Functional  Interrelation  of  the  Organs  of  Internal  Secretion 55 


viii  CONTENTS 


CHAPTER   IV. 


Pathology. 

Benign  Tumors 60 

Parenchymatous  Goiters 60 

Colloid  Goiter 61 

Fetal  Adenoma 64 

Malignant  Tumors 65 

Epithelial  Tumors 67 

Malignant  Adenoma  or  Proliferating  Goiter 67 

Carcinoma 70 

Metastatic  Colloid  Goiter 70 

Parastruma  or  Glycogen-containing  Goiter 72 

Postbranchial  Goiter 73 

Papilloma 74 

Cancroid 76 

Tumors  of  Connective-tissue  Origin                       77 

Fibrosarcoma 77 

Polymorphous-cell  Sarcoma 78 

Round-cell  Sarcoma            78 

Myxosarcoma 79 

Endothelioma 79 

Perithelioma 80 

Combination  of  Various  Forms  of  Malignant  Goiter 80 

Mixed  Tumors 80 

Dermoids  and  Teratoma 81 

Accessory  Goiters 82 

Median  Cysts 83 

Lingual  Goiter 85 

Intrathoracic  Accessory  Goiter ....  86 

Ovarian  Goiter 87 


CHAPTER  V. 

Inflammations  of  the  Thyroid. 

History 89 

Bacterial  Thyroiditis 90 

Etiology 93 

Pathology 95 

Symptoms 95 

Diagnosis 98 

Prognosis 101 

Treatment 102 

Toxic  Thyroiditis 103 

Tuberculosis  of  the  Thyroid 106 

Follicular 106 

Caseous 106 


COXTEXTS  ix 

Syphilis  of  the  Thyroid 108 

Woody  Thyroiditis^ 109 

Parasitic  Thyroiditis ill 

Hydatid  Cyst  of  the  Thyroid 113 

Congestions  of  the  Thyroid .114 

Pathological  Anatomy 115 

Symptoms 115 

Treatment 115 

1  raumatic  Lesions  of  the  Thyroid 115 

Contusions 116 

Wounds 116 

Treatment 117 

CHAPTER   VI. 

Anatomopathological  Relations  of  Goiter  to  the  Surrounding  Structures. 

Relation  of  Goiter  to  Skin  and  Muscles 119 

Relation  of  Goiter  to  the  Larynx  and  Trachea 120 

Relation  of  Goiter  to  the  Pharynx  and  Esophagus 123 

Relation  of  Nodular  Goiter  to  Bloodvessels 124 

Relation  of  Goiter  to  Nerves 125 


CHAPTER   VII. 

Clinical  Symptoms  and  Diagnosis. 

Clinical  Symptoms 126 

Mechanical  Symptoms .126 

Dyspnea 126 

Dysphagia 127 

Symptoms  Due  to  Injun'  of  the  Inferior  Laryngeal  Nerve     ....  .128 

Functional  Symptoms 130 

Diagnosis  of  Goiter 130 

Is  the  Tumor  Developed  in  the  Thyroid?  150 

Laryngoscopic  Examination 131 

What  is  its  Nature? 132 

( roiter-heart         133 

I  he  Mechanical  Goiter-heart 133 

The  Thyrotoxic  Goiter-heart 136 


CHAPTER   VIII. 

Intrathoracic  ( Ion  1  u. 

Relation  of  Intrathoracic  Goiter  to  Neighboring  Hssues 14- 

Symptoms '13 

Diagnosis '3- 

Differential  Diagnosis '55 

Prognosis '59 


x  CONTENTS 

CHAPTER   IX. 

Goiter  Death 160 

CHAPTER   X. 

Circular  Goiter. 

Symptoms 163 

Diagnosis 163 

Treatment 164 

Retrotracheal  or  Retro-esophageal  Goiter 165 

Intratracheal  Goiter 165 

CHAPTER  XI. 

Congenital  Goiter  and  Goiter  in  Children. 

Congenital  Goiter 166 

Symptoms 167 

Treatment 168 

Goiter  in  Children 169 

CHAPTER  XII. 

Simple  Goiter  and  Pregnancy. 

Treatment 171 

CHAPTER  XIII. 

Clinical  Aspect  of  Malignant  Goiters. 

Relations  to  Surrounding  Structures 173 

Course  and  Symptoms 175 

Diagnosis 178 

Treatment 179 

Hypothyroidism — Myxedema 182 

Synonyms 182 

The  Kocher-Reverdin  Controversy 182 

Etiological  Relationship  between  the  Various  Forms  of  Hypothyroidism  .  187 

Nomenclature 189 


CONTEXTS 


XI 


CHAPTER  XIV. 

Pathology  of  the  Various  Forms  of  Thyroid  Insufficiency. 

Thyroid ioj 

Skin ig2 

Osseous  Svstem  103 

Nervous  System 104 

Vascular  System 195 

Genital  Apparatus ".  195 

Surgical  Athyroidism  and  Surgical  Cachexia  Strumipriva 196 

Symptoms 196 

Spontaneous  Adult  Hypothyroidism 198 

Etiology 198 

Symptoms 200 

CHAPTER  XV. 

Congenital  Athyroidism,  Spontaneous  Infantile  Hypothyroidism,  and 

Cretinism. 

Etiology  of  Congenital  Athyroidism  and  Spontaneous  Infantile  Hypothyroidism  203 

Cretinism.     Etiology 204 

Symptoms  of  Congenital  Athyroidism,  Spontaneous  Infantile  Hypothyroidism  207 

Differential  Diagnosis 210 


CHAPTER  XVI. 

Small  Thyroid  Insufficiency 


216 


CHAPTER   XVII. 


uctuation 


( loiter 


s  of  ( loiter 


Etiology  of  Endemic  Goiter  and  Cretinism 

Historical 

Geographical  Distribution  of  Endemic  Goiter  and  Cretinism   . 
Economical,  Social  and  Military  Significance  of  Endemic  Goiter  and 

Goiter  Epidemics 

Fluctuations  of  Endemic  Goiter     .... 
Fluctuations  of  Cretinism 

Conclusions  Drawn  from  the  Study  of  the  F 

<  inner  in  Animals 

rheories  Regarding  the  Etiology  of  Goiter    . 

I  he  Relation  between  Water  and  Endemic 

I  [ydrotelluric  Theory 

Rt  pm's  or  Plutonian  I  heory  . 

Radio-active  Wants  and  Goiter 

<  Organic  Theory  .... 
Contagion  1>\  Contact  Theory 
Infection  I  heory     .... 

<  '•'  neral  Conclusions 


Ci 


(.  '1  ei  inism 


220 
221 

--7 
228 
232 

234 
235 
236 
241 
242 
249 
250 

263 

272 
275 


xii  CONTEXTS 


CHAPTER  XVIII. 

Medical  Treatment  of  Simple  Goiter. 

Prophylaxis 276 

Medical  Treatment  of  Goiter 277 

Indications  for  Medical  Treatment 277 

Contra-indications  to  Medical  Treatment 278 

Medicaments 279 

Iodin  in  Treatment  of  Goiter 279 

Crotti's  Formula  for  Treatment  of  Non-toxic  Parenchymatous  Goiter       .  281 

Dangers  of  Iodin  Medication 282 

Treatment  of  Thyroid  Insufficiency 283 

Thyroid  Opotherapy         283 

Dangers  of  Thyroid  Opotherapy    ....  283 

Ingestion  Method 285 

Polyglandular  Treatment 290 


CHAPTER  XIX. 
Thyroid  Grafting       ....  ...     291 

CHAPTER  XX. 

Indications  for  Operation  in  Simple  Goiter. 

Contra-indications  to  Operation 299 

Treatment  with  Injections 3°° 

Thyrotoxicosis 3°3 

History 3°3 

CHAPTER  XXI. 

Cardiovascular  Symptoms. 

Differential  Diagnosis  of  Thyrotoxic  Tachycardia 304 

Etiological  Explanation  of  Tachycardia 3°6 

Palpitation 3°7 

Thyrotoxic  Heart 3C7 

Thyrotoxic  Pulse 3°9 

Test  of  Functional  Capacity  of  the  Heart 3l° 

CHAPTER  XXII. 

Basedow  Struma. 

Vascular  Symptoms  of  the  Thyroid 3J3 

Pathology  and  Histology  of  Thyrotoxic  Goiter 3X5 


CONTENTS  xiii 


CHAPTER  XXIII. 

Ocular  Symptoms. 

Exophthalmos 310 

Unilateral <?tq 

Bilateral 320 

Eyelid  Symptoms 322 

Dallrymple 322 

Graefe 322 

Kocher 323 

Stellwag 324 

Moebius 324 

Lachrymal  Secretion .  ....  325 

Staring  Look 325 

Edema  and  Pigmentation  of  the  Eyelids 326 

Etiology  of  Exophthalmos 326 


CHAPTER  XXIV. 

Mi.'scular  Symptoms. 

Tremor ....331 

Great  Muscular  Fatigue 332 

Sudden  Giving  Way  of  the  Knees 333 

Muscular  Cramps 333 

Tendinous  Reflexes 333 


CHAPTER  XXV. 

Nervous  and  Mental  Symptoms  in  Basedow's  Disease. 

Heredity  of  Graves'  Disease 338 

CHAPTER  XXVI. 

Digestive  Disturbances. 

Appetite 340 

Nausea -,40 

Gastric  Flatulence ^40 

Vomiting ^40 

Diarrhea ^41 

Icterus 341 

CHAPTER  XXVII. 
Genital  Disturbances (42 


xiv  CONTEXTS 


CHAPTER  XXVIII. 

Respiratory  Disturbances. 

Bryson  Symptom 343 

Shortness  of  Breath 343 

Coughing        344 

Hoarseness 344 

CHAPTER  XXIX. 

Sensory  Disturbances  and  Insomnia. 

Pains 345 

Headache 345 

Vertigo 346 

Tingling  and  Numbness .      .  346 

Insomnia 346 

CHAPTER  XXX. 

Cutaneous  Symptoms. 

Sensation  of  Heat 347 

Dermographism 347 

Hyperhydrosis 347 

Itching  of  the  Skin 347 

Urticaria 348 

Falling  of  the  Hair .                   .  348 

Brown  Pigmentation  of  the  Skin , 348 

Edema 348 

CHAPTER  XXXI. 
Blood  Changes  in  Basedow's  Disease. 

Coagulability  of  the  Blood 352 

Adrenalinemia 353 

Hyperglycemia 354 

Antitrypsin  Content  of  the  Blood 354 

Complement-fixation 354 

CHAPTER  XXXII. 

Disturbances  in  Metabolism. 

Loss  of  Flesh 355 

Temperature 355 

Glycosuria  and  Diabetes  in  Graves'  Disease 356 

Alimentary  Glycosuria 356 

Polyuria 357 

Polydipsia 358 

Albuminuria 358 

Thyrotoxicosis  is  a  Chronic  Disease 358 

Fulminating  Forms  of  Graves'  Disease 358 

All  the  Thyrotoxic  Symptoms  are  Worse  in  the  Morning 359 


COXTEXTS  xv 

CHAPTER  XXXIII. 
Fruste  Forms  of  Hyperthyroidism  or  Small  Hyperthyroidism. 

Fruste  Forms  of  Hyperthyroidism 361 

Obscure  Forms  of  Hyperthyroidism 362 

CHAPTER  XXXIV. 

Hyperthyroidism  and  Hypothyroidism 363 

CHAPTER  XXXV. 

Infantile  and  Juvenile  Hyperthyroidism         ....  365 

CHAPTER  XXXVI. 

Exophthalmic  Goiter  in  Pregnancy. 

Treatment 368 

CHAPTER  XXXVII. 
Etiology  of  Graves'  Disease. 

Graves'  Disease  a  Thyro-neuro-poh  glandular  Disease 372 

(A)  Thyrogenetic  Origin  of  Graves'  Disease 372 

Hypothyroidism  vs.  Hyperthyroidism 372 

Pathological  Arguments 375 

Experimental  Arguments 376 

Arguments  Derived  from    I  hyroid  Opotherapy  in  Human  Beings  379 

Surgical  Argument 381 

(B)  Nervous  Origin 382 

\  egetative  Nervous  System 385 

(C)  Polyglandular  Origin 388 

I  hyroid  and  Hypophysis 389 

Thyroid  and  the  Genital  System 389 

1  hyroid;   Pancreas;  Adrenals 390 

I  hyroid  and  Thymus 392 

I  hyroid  and  Parathyroids JQJ 

Conclusions 592 

Iodin-Basedow 393 

Is  There  any  Relation  between   Iodin-Basedow  and  the  Quantity  of   [odin 

Absorbed: 394 

I  he  Relation  between  Basedow's  Disease  and  Thyroiditis J96 

Graves'  Disease  is  a  Toxic  Thyroiditis J99 

Hyperthyroidism 400 

I  )\  sth)  roidism 401 

Part  of  the  Thyrotoxic  Symptoms  Ma)    Be  of  Anaphylactic  Origin  402 

Why  is  it  that  Some  People  I  l.i  ve  Exophthalmic  ( Joiter  and  <  Ithers  I  )<>  Not ;  40; 

Summary  of  Conclusions  Concerning  the  Etiology  of  Graves'  Disease  403 


xvi  CONTENTS 

CHAPTER  XXXVIII. 

Treatment  of  Graves'  Disease. 

Lipoids      .  405 

Is  There  Truly  a  Medical  Treatment  for  Graves'  Disease? 407 

Results  of  Medical  Treatment 408 

Medical  Cases 410 

Conclusions 411 

When  Shall  We  Consider  a  Patient  Cured? 415 

Medical  Treatment 417 

Rest  Cure 417 

Medication 419 

Diet 420 

Hydrotherapy .  421 

Electrotherapy 421 

General 421 

Local 421 

Galvanic 421 

Electrolysis 422 

Radiotherapy 422 

Serotherapy 426 

Antithyroid  Chymotherapy 426 

Thyrotoxic  Serotherapy 427 

Polyglandular  Medication 427 

Thymus  Opotherapy 428 

Hypophysis  Opotherapy 428 

Parathyroid  Opotherapy 428 

Adrenalin 428 

Pancreas  Opotherapy 428 

Crotti's  Treatment  for  Exophthalmic  Goiter 428 


CHAPTER  XXXIX. 

Indications  and  Contra-indications   for  Surgical  Treatment  of  Exophthalmic 

Goiter. 

What  Line  of  Conduct  Shall  We  Follow  in  Deciding  the  Course  of  Treatment  in 

Each  Given  Case? 434 


CHAPTER  XL. 
Surgical  Technic  of  Operations  upon  the  Thyroid  Gland. 

Surgical  Technic 439 

Anatomical  Facts 440 

Pathological  Planes  of  Cleavage 442 

Blood  Supply  of  the  Thyroid 442 

Parathyroids 445 

Recurrent  Laryngeal  Nerves 447 


COXTEXTS  xvii 

Conclusions  Drawn  from  Anatomical  Facts 448 

Excision,  Resection,  or  Enucleation  ? 448 

Excision 449 

Resection 449 

Enucleation 450 

Shall  the  Operation  be  Unilateral  or  Bilateral? 454 

How  Much  Thyroid  Tissue  Can  Safely  Be  Removed? 457 

Shall  We  Dissect  the  Parathyroids? 458 

Ligations 458 

What  is  the  Point  of  Election  for  Ligation? 462 

Technic  of  Ligations 463 

Isolated  Ligation  of  the  Superior  Pole 464 

Technic  for  the  Isolated  Ligation  of  the  Inferior  Thyroid  Artery      ....  464 

Isolated  Ligation  of  the  Inferior  Thyroid  on  the  Inner  Border  of  the  Scalenus  465 

Hemostasis 466 


CHAPTER  XLI. 

Operative  Technic  for  Thyroidectomy-. 

Incision 469 

Operation  for  Intrathoracic  Goiter 475 

Technic  of  Operations  for  Malignant  Goiters 477 


CHAPTER  XLII. 

Operative  Accidents. 

Lesions  of  the  Nerves 478 

Suffocation  and  Collapse  of  the  Trachea         479 

Injury  to  the  Trachea,  Esophagus  and  Pleura 481 

Tracheotomy 481 

Air  Embolism 481 


CHAPTER  XLIII. 

Sympathectomy. 

Pathology 483 

Immediate  Results  of  the  Operation 483 

Remote  Results 484 

Choice  of  ( Operation 484 

Surgical  Technic  for  Sympathectomy 4S5 


CHAPTER  XLIV. 

Canthorraphy 487 

CHAPTER   XLV. 

Bnil.lNC-u  VII  K    I  NJECTIONS. 
Technic 48S 


xviii  CONTENTS 

CHAPTER  XLVI. 

Preoperative  Treatment  of  the  Patient 489 

CHAPTER  XLVII. 

Operating  Room  Technic 491 

CHAPTER  XLVIII. 

Postoperative  Treatment 493 

CHAPTER  XLIX. 

Anesthesia. 

Chloroform,  Ether,  or  Nitrous  Oxide? 498 

Local  Anesthesia S01 

Technic  of  Local  Anesthesia 502 

Intratracheal  Insufflation  Anesthesia  in  Thyroid  Surgery 506 

Pantopon-scopolamin 5°7 

CHAPTER  L. 

Postoperative  Complications. 

Shock 5°9 

Vasomotor  Exhaustion  and  Paralysis 509 

Cardiac  Spasm  and  Eventual  Failure 511 

Inhibition  of  the  Function  of  all  Organs 511 

Deficiency  of  Carbon  Dioxide  in  the  Blood,  or  Acapnia 511 

Morphological  Changes  in  the  Ganglion  Cells 511 

Loss  of  Vasomotor  Control 512 

Primary  Suprarenal  Exhaustion S12 

Treatment  of  Shock  and  Hemorrhage 5J5 

Crotti's  Technic  of  Indirect  Transfusion         518 

Postoperative  Hyperthyroidism 5J9 

Acidosis 521 

Postoperative  Fever •  523 

Postoperative  Tetany 524 

Symptoms 524 

Chvostek 525 

Weiss 525 

Trousseau S2^ 

Erb 52» 


COXTEXTS  xix 

How  Many  Parathyroids  May  Be  Removed  before  Tetany  Appears?      ....  529 

Prognosis 530 

Treatment  of  Tetany 531 

Grafting  of  the  Parathyroids 532 

Pulmonary  Complications 533 

Postoperative  Dysphagia 534 

Postoperative  Hematoma 534 

Raising  of  the  Scar 534 

After-treatment         534 

Rules  for  Goiter  Patients 535 


CHAPTER  LI. 

The  Thymus  Gland. 

Synonyms 536 

History  and  Etymology 536 

Embryology 536 

Histology 537 

Surgical  Anatomy  of  the  Thymus 537 

Involution  of  the  Thymus 539 

Experimental  Pathology  of  the  Thymus 540 

Skeleton 540 

Nervous  System 540 

Muscular  System 541 

Interrelation  of  the  1  hymus  to  the  Organs  of  Internal  Secretion 541 

Status   1  hymolymphaticus ^42 

1  hymic  Tracheostenosis 54.2 

Acute  Symptoms 54} 

Chronic  Form  of  1  hymic  Hyperplasia 543 

Explanation  of  the  Choking  Spells  and  of  Thymic  Death 545 

Pressure  at  the  Superior  Opening  of  the  Thorax 54^ 

Pressure  in  the  Thorax 546 

Spasm  of  the  Glottis 546 

Diagnosis  of  1  hymus  Hyperplasia 54S 

X-ray  Characteristics  of  1  hymic  Hyperplasia 550 

Differential  Diagnosis  of  Thymic  Hyperplasia 550 

Relation  of  Thymic  Hyperplasia  to  Basedow's  Disease 551 

I  hymogene  Basedow 553 

Differential  Diagnosis  between  Thymic  and   Thyroid  Basedow 553 

I  natment  of  Thymic  Hyperplasia  Complicating  Graves'  Disease 555 

Treatment  of  Thymic  Hyperplasia  in  Children  556 


CHAPTER   LIE 

Surgical  Technic  of  Thymectomy. 

Anesthesia 557 

Surgical  Technic 557 


DISEASES  OF  THYROID  AND  THYMUS. 


CHAPTER   I. 
ANATOMY  AND  EMBRYOLOGY. 

ANATOMY. 

The  thyroid  gland  is  an  unpaired  gland  of  reddish  color.  It  lies 
upon  the  lateral  surface  of  the  thyroid  and  cricoid  cartilages  and  upon 
the  anterolateral  surface  of  the  upper  end  of  the  trachea  which  it 
surrounds  like  a  horsehoe. 

The  thyroid  gland  consists  of  two  lobes  united  by  a  narrow  trans- 
verse portion,  the  isthmus.  The  lobes  are  conical  in  shape,  and  measure 
about  2  inches  in  length,  i\  inches  in  width,  and  f  inch  in  thickness. 
The  gland  in  toto  weighs  about  an  ounce.  It  must  be  well  under- 
stood that  these  figures  may  vary.  There  are  countries  where  the 
general  average  weight  may  be  higher  than  the  one  just  given,  and 
vet  the  gland  will  still  be  normal.  It  is  customary  to  call  the  upper 
portion  of  a  lobe  upper  pole,  and  the  lower  portion  lozver  pole, 
while  the  portion  of  the  gland  between  the  upper  and  lower  poles  may 
be  called  the  body  of  the  gland.  Inwardly,  each  lobe  comes  in  con- 
tact with  the  trachea,  esophagus,  thyroid  and  cricoid  cartilages,  the 
inferior  laryngeal  nerve,  the  inferior  constrictor  of  the  pharynx,  and  the 
posterior  part  of  the  cricothyroid  muscle.  Its  posterior  surface  is  in 
relation  with  the  carotid  sheath  containing  the  common  carotid,  the 
internal  jugular  vein  and  the  vagus  nerve;  it  is  furthermore  in  relation 
with  the  inferior  thyroid  artery,  with  the  parathyroids,  and  also  with 
the  prevertebral  fascia  and  muscles.  The  anterolateral  surface  is  cov- 
ered by  the  sternothyroid,  the  sternohyoid  and  the  omohyoid  muscles; 
the  sternocleidomastoid  muscles  overlap  the  outer  border  of  the  gland. 

The  isthmus  is  situated  in  front  of  the  trachea  and  covers  its  second, 
third  and  sometimes  its  fourth  ring.  It  varies  in  size  and  width. 
Usually,  it  measures  about  half  an  inch  in  breadth  and  the  same  in  depth. 
It  may  even  cover  the  cricoid  cartilage,  or  at  least  part  of  it.  In  such 
cases  superior  tracheotomv  presents  some  difficulties.  The  isthmus 
may  be  absent  altogether  (Fig.  i),  or  may  be  entirely  separated  from 
both  lobes,  thus  forming  a  lobe  by  itself. 
2 


18 


AX  ATOMY  AXD  EMBRYOLOGY 


From  the  isthmus,  or  from  the  adjacent  part  of  either  lobe,  a  narrow 
strip  of  glandular  tissue  is  often  seen  passing  in  front  of  the  thyroid 
cartilage  upward  toward  the  body  of  the  hyoid  bone  to  which  it  may  or 


Fig.    I. — Thyroid    without    isthmus    and 
without  pyramidal  process. 


Fig.    2. — Thyroid    with    one    pyramidal 
process. 


may  not  be  attached.  The  process  is  called  the  pyramidal  process 
(Fig.  2).  It  is  not  constant  and  is  found  oftener  on  the  left  side  than  on 
the  right.     In  rare  cases  the  pyramidal  process  may  be  double  (Fig.  3). 


Fig.  3. — Thyroid  with   two  pyramidal 
processes. 


Fig.    4. — Thyroid    gland    whose    isthmus 
does  not  join   the  two  lobes. 


It  has  the  same  structure  as  the  thyroid  gland.     The  pyramidal  process 
represents  the  vestiges  of  the  thyroglossus  duct  (Fig.  4). 

The  thyroid  gland  is  in  close  connection  with  the  trachea  and  with 
the  larynx  by  interwoven  connective  tissue.     It  has  special  attachment 


ANATOMY  19 

with  the  cricoid  cartilage  through  bands  of  fibrous  tissue  extending 
from  the  isthmus  and  lateral  lobes  to  the  cricoid  cartilage.  These 
bands  are  known  as  the  suspensory  ligaments  of  the  thyroid.  It  is  on 
account  of  such  relation  that  the  latter  organ  follows  the  movements 
of  the  larynx  during  deglutition. 

The  entire  thyroid  gland  may  be  wholly  absent,  but  this  is  very  rare 
indeed. 

Accessory  thyroids  are  frequently  found  in  the  neck.  They  are  more 
common  in  the  neighborhood  of  the  hyoid  bone,  but  they  mav  be  found 
below  the  thyroid  gland  as  far  down  as  the  arch  of  the  aorta  and  the 
bifurcation  of  the  trachea.  They  have  the  same  histological  structure 
as  the  thyroid  gland  itself;  the)'  mav  contain  colloid  or  mav  show 
embrvonical  structure.  Goiter  or  tumors  of  any  kind  can  develop  from 
them. 


A    a. 


Fig.  5. — 1,  common  carotid;  2,  internal  jugular  vein;  3,  superior  thyroid  artery  and 
vein.  Normally  the  artery  originates  a  little  higher  up  from  the  external  carotid  and 
not  from  the  common  carotid,  as  wrongly  shown  by  the  picture;  4,  middle  vein;  5,  imae 
veins;  6,  inferior  thyroid  artery;  7  and  8,  right  innominate  veins;  9,  aorta. 

Blood  Supply.  1  he  thyroid  gland  receives  its  blood  supply  from 
three  arteries,  the  superior,  the  inferior,  and  the  ima  artery  (Fig.  5). 
The  superior  thyroid  artery  is  the  first  branch  of  the  external  carotid. 
It  runs  in  a  curve  forward  and  downward  to  the  upper  pole,  and  gives 
off  a  branch  for  the  hyoid  bone,  one  for  the  sternocleidomastoid  muscle, 
one  for  the  larynx  (the  superior  laryngeal  artery  which  perforates  the 
thyrohyoid  membrane),  and  one  branch  known  as  the  cricothyroid 
artery,  passing  in  front  of  the  cricothyroid  ligament  just  above  the 
isthmus.  The  artery  finally  splits  into  two  terminal  branches  in  the 
upper  pole  of  the  thyroid  gland,  the  anterior  and  posterior  branches. 


20  ANATOMY  AND  EMBRYOLOGY 

The  inferior  thyroid  artery  arises  from  the  thyrocervical  trunk  given 
off  by  the  subclavian  artery.  It  runs  in  front  of  the  scalenus  anticus 
muscle,  at  first  upward,  then  bends  inwardly,  passing  behind  the 
carotid  sheath,  and  terminates  in  the  posterior  surface  of  the  thyroid 
gland. 

The  ima  artery  comes  off  directly  from  the  arch  of  the  aorta  or  from 
the  innominate  artery  and  terminates  in  the  isthmus.     It  is  not  constant. 

Anna  Begoune  has  demonstrated  that  each  artery  supplies  a  terri- 
tory of  its  own;  the  superior  thyroid  artery  supplies  the  superior  half 
of  the  lobe;  the  inferior  thyroid  artery  supplies  the  inferior  half  of  the 
lobe.  This  is  of  course  very  schematic  and  not  literally  true,  as  both 
territories  exchange  very  numerous  anastomoses,  which  in  time  may 
grow  into  an  important  collateral  circulation.  If  the  four  arteries  are 
injected,  not  only  the  whole  thyroid  gland,  but  also  the  adjoining 
organs,  as  the  trachea  and  the  esophagus,  will  become  injected  at  the 
same  time.  This  is  an  important  fact,  as  it  shows  that  after  ligation  of 
all  the  thyroid  arteries,  the  gland  may  still  receive  some  blood  from  its 
collateral  circulation. 

The  veins  of  the  thyroid  gland  show  considerable  variation.  They 
form  a  rich  plexus  upon  and  beneath  the  capsule  of  the  gland.  The 
superior  thyroid  vein  terminates  generally  in  the  thyrohnguofacial 
trunk  formed  by  the  junction  of  the  thyroid,  lingual  and  facial  veins. 
The  inferior  thyroid  vein  empties  into  the  internal  jugular  vein.  Not 
infrequently,  as  shown  by  Kocher,  there  is  a  middle  vein  which  emerges 
from  the  side  of  the  gland,  passes  transversely  outward  and  empties 
into  the  internal  jugular  vein.  From  the  lower  border  of  the  isthmus 
and  both  poles  there  is  a  plexus  of  two,  three  or  more  veins  which  go 
directly  downward  and  empty  into  the  innominate  vein  of  both  sides. 
They  are  known  as  the  imce  veins  (Fig.  5). 

Thyroid  veins  have  no  valves. 

These  numerous  bloodvessels,  be  they  arterial  or  venous,  pass  to  and 
fro,  penetrate  the  gland,  and  break  into  smaller  branches.  They  ulti- 
mately form  a  capillary  network  around  each  follicle  and  come  in  close 
contact  with  each  cell. 

The  blood  supply  of  the  thyroid  gland  is  very  extensive,  and  in  pro- 
portion to  its  size,  the  circulation  here  is  more  extensive  than  in  the 
brain.  This  abundant  circulation  shows  that  the  function  of  the  thy- 
roid gland  must  be  an  important  one. 

Lymphatics. — Forming  a  network  around  each  vesicle,  the  small 
lymphatics  resolve  themselves  into  larger  collecting  trunks  which  empty 
either  into  the  prelaryngeal  group  of  lymph  nodes  located  in  front  of  the 
cricothyroid  membrane,  or  into  the  cervical  group  all  along  the  com- 
mon carotid,  or  into  the  pretracheal  group  below  the  isthmus.     Some  of 


HISTOLOGY  21 

these    deeper   trunks  empty   into   the   lymph   nodes   along  the  postero- 
lateral surface  of  the  pharynx  and  esophagus. 

The  nerve  supply  comes  from  the  sympathetic  (median  and  inferior 
cervical  ganglion)  and  from  the  vagus  nerve  (superior  laryngeal  branch). 
The  inferior  laryngeal  nerve  comes  in  close  contact  with  the  gland  but 
does  not  supplv  it.    The  capsule  of  the  thyroid  contains  sensory  nerves. 

HISTOLOGY. 

The  thyroid  gland  has  no  excretory  canal;  it  belongs  to  the  group 
of  glands  of  internal  secretion.  Although  this  is  true,  we  must,  how- 
ever, admit  that  the  secretion  of  the  thyroid  still  affects  the  external 
type,  since  the  products  of  cellular  secretion  empty  into  the  alveoli 
under  the  form  of  colloid,  and  are  only  later  absorbed  into  the  general 
circulation.  We  have,  consequently,  two  distinct  processes:  one  of 
secretion  and  the  other  of  absorption.  The  thyroid  gland  is  composed 
of  connective  tissue  and  epithelium. 

The  connective  tissue  forms  a  capsule  which  surrounds  the  entire 
gland,  and  projects  inward,  prolongations  dividing  the  gland  into  lobes 
and  lobules.  These  lobes  contain  round,  tubular,  sacculated,  branching 
or  prismatic  vesicles  or  follicles,  each  one  separated  b}*  more  slender 
septa.  In  this  stroma,  be  it  interlobular  or  interfollicular,  elastic  fibers, 
nerves,  blood  and  lymphatic  vessels  are  found.  The  normal  size  ot  the 
alveoli  varies  from  50  to  300 m-  It  is  not  quite  uncommon  to  find  in  it 
small  foci  of  lymphoid  tissue. 

The  epithelium  is  cuboidal  or  cylindrical,  and  is  arranged  in  one 
layer  all  around  the  wall  of  the  follicle.  The  follicle  in  the  thyroid  gland 
has  no  membrana  propria.  Wegelin,  however,  has  shown  that  a  membrana 
propria  exists  in  goiter,  especially  in  cases  where  hyahn  degeneration  is 
present.  Each  cell  is  provided  with  a  single  oval-shaped  or  round  nucleus 
which  contains  a  thin  chromatin  network  with  one  or  more  chromatin 
corpuscles.  The  diameter  of  each  nucleus  is  generally  from  5  to  6/z. 
Acidophiles  granulations  and  fat  are  found  in  the  cells. 

Two  types  of  cells  are  usually  described  in  the  thyroid  vesicles: 
the  "  chief  cells,"  far  more  numerous,  clear  and  finely  granular,  and  the 
"colloid  cells,"  more  opaque  and  granular.  Differences,  however, 
between  these  two  varieties  are  not  sufficient  to  warrant  differentiating 
them  into  two  distinct  types  of  cells.  The  colloid  cells  seem  to  be 
merely  chief  cells  loaded  with  colloid  material  which  has  not  yet  been 
excreted  into  the  alveolar  lumen.  For  the  majority  ot  the  thyroid 
cells,  the  secretion  affects  the  merocrine  type.  This  means  that  a  part 
only  of  the  cell  is  used  by  the  secreting  process.  Once  elaborated,  the 
secretion  is  evacuated  into  the  alveolar  lumen  by  the  breaking  open  oi 


22  ANATOMY  AXD  EMBRYOLOGY 

the  nuclear  membrane;  then  the  cells  regenerate  and  become  "chief 
cells,"  ready  to  start  over  the  secreting  cycle.  In  numbers  of  other 
instances,  however,  the  secretion  affects  the  holocrine  type.  In  these 
cases  the  whole  cell  is  used  for  colloid  production.  Nothing  remains 
afterward,  the  whole  cell  is  destroyed. 

Colloid. — Some  follicles  are  without  lumen.  The  majority,  however, 
contain  colloid  substance.  Colloid  may  be  fluid  or  thick.  This  differ- 
ence in  consistency  is  due  to  the  difference  in  concentration  of  the 
albuminous  substances.  When  filled  with  thick  colloid,  the  follicle 
seems  to  be  distended,  and  when  it  contains  fluid  colloid,  the  follicle 
does  not  seem  to  be  under  tension. 

The  staining  power  of  colloid  is  exceedingly  variable.  In  the  same 
microscopic  field  it  is  not  rare  to  find  alveoli  in  which    the  colloid   did 


t  W  «  &  ^ 


Fig.  6. — Colloid  with  its  vacuoles.      X  350. 

not  stain  at  all  and  others  which  did  take  the  staining  in  the  most  intense 
manner.  We  may  say  in  a  general  way  that  the  thicker  the  colloid, 
the  more  it  will  stain,  although  this  is  not  always  true,  as  solid  lumps  of 
colloid  are  not  so  rarely  seen  in  which  the  staining  has  scarcely  taken. 

The  thick  or  solid  colloid  looks  homogeneous,  and  must  be  regarded 
as  a  product  which  does  not  absorb  as  readily  as  thin  colloid.  It  is 
quite  common  to  find  vacuoles  in  the  colloid  (Fig.  6).  These  vacuoles 
are  often  artefacts  due  to  retraction  of  the  colloid  substance  when  it 
undergoes  coagulation.  These  vacuoles  are  then  located  at  the  per- 
iphery of  the  coagulum  and  remain  in  connection  with  the  walls  of  the 
follicle  through  very  thin  trabecules.  Oftentimes,  however,  they  are 
due  to  the  presence  of  fat  and  mucine  in  the  colloid.  They  are  then 
more  or  less  in  the  center  of  the  colloid. 

The  colloid  most  generally  enters  the  general  circulation  through  the 


EMBRYOLOGY  23 

lymphatic  spaces  and  vessels  surrounding  each  follicle.  These  lymphatics 
often  contain  a  substance  with  atypical  staining  qualities  similar  to  the 
ones  of  colloid.  That,  however,  this  substance  is  identical  with  the 
colloid  is  not  yet  an  absolute,  demonstrated  fact. 

The  amount  of  colloid  found  in  a  gland  is  by  no  means  a  true  index 
of  the  functional  activity  of  the  thyroid.  In  the  newborn,  and  in 
Graves'  disease  the  amount  of  colloid  found  is  scant.  The  same  is  true 
in  acute  infectious  diseases;  there  the  colloid  is  diminished  in  direct 
proportion  to  the  severity  of  the  disease.  Nobody,  I  presume,  will 
contend  that  in  these  conditions  the  functional  activity  of  the  gland  is 
diminished.  Everything  seems  to  disprove  it;  the  experimental  as 
well  as  the  microscopic  findings  and  especially  the  increased  blood 
supply.  On  the  other  hand, -the  colloid  is  increased  in  conditions  where 
we  know  the  functional  activity  of  the  gland  is  diminished,  as  in  colloid 
goiter  and  in  hypothyroidism.  Why  such  apparent  discrepancies  ? 
Because,  beside  "secretion"  there  is  another  phenomenon  just  as 
important  and  that  is  "absorption."  The  amount  of  colloid  found  in  a 
gland  depends  upon  these  two  processes,  and  the  physiological  activity 
of  the  thyroid  depends  largely  upon  the  equilibrium  between  them. 
For  instance,  we  may  find  very  little  or  no  colloid  in  an  extremely  active 
gland,  because  there  is  at  the  same  time  a  rapid  absorption  of  the  thy- 
roid products  going  on.  On  the  other  hand,  the  quantity  of  colloid 
may  be  found  materially  increased  in  cases  where  secretion  and  absorp- 
tion are  diminished.  In  these  two  instances  we  would  draw  false  con- 
clusions as  to  the  functional  activity  of  the  gland,  if  we  should  judge  it 
only  by  the  amount  of  colloid  found.  One  thing,  however,  seems  to  be 
certain:  the  amount  of  colloid  and  especially  its  consistency  seems  to 
be  in  direct  relation  with  the  increased  vascularization.  This  is  not 
only  true  in  Graves'  disease,  in  acute  infectious  processes,  in  thyroids 
of  newborn  babies,  but  has  also  been  shown  experimentally.  With 
increased  blood  supply  the  colloid  loses  its  thickness  and  becomes 
readily   absorbable. 

Desquamation. — Normally,  a  few  cells  may  decay,  lose  their  connec- 
tion with  alveolar  walls,  and  fall  into  the  lumen  of  the  alveoli  where  they 
will  gradually  disintegrate  and  be  eliminated.  These  desquamated  cells 
are  replaced  by  new  ones.  In  pathological  processes,  especially  in  severe 
thyrotoxicosis,  desquamation  may  be  very  marked.  As  a  rule  it  is 
always  accompanied  with  thinning  or  absence  of  the  colloid.  It  is  always 
ot  severe  prognosis. 

EMBRYOLOGY. 

I  he  thyroid  is  primarily  a  dependence  of  the  esophagus  (tuniciers 
ammocetes)  and  in  its  endostyle  form  is  ;i  digestive  gland  of  great  impor- 


24  ANATOMY  AND  EMBRYOLOGY 

tance  through  its  external  secretion.  In  its  ductless  form  it  is  only  the 
atrophic  remnant  of  its  ancestor,  which,  while  it  has  suffered  a  corre- 
sponding distortion  of  function,  still  profoundly  influences  the  animal's 
nutrition  through  the  effects  of  its  internal  secretion. 

The  thyroid  gland  is  found  in  the  anterior  portion  of  the  neck  of 
every  vertebrate  animal.  It  is  absent  in  the  amphioxus.  It  originates 
from  an  unpaired  formation,  the  tuberculum  impar  of  His,  which  is 
formed  in  the  middle  line  by  an  evagination  of  the  epithelium  of  the 
anterior  pharyngeal  wall,  at  the  level  of  the  second  branchial  arch,  in 
or  slightly  anterior  to  the  first  aortic  arch.  For  a  long  time  it  was 
thought  that  the  thyroid  gland  had  a  double  origin  and  was  formed  by 
the  fusion  of  the  median  and  lateral  thyroids,  originating  from  the 
median  and  lateral  "anlagen."  However,  Miiller,  His,  Verdin,  and 
Tourneux,  after  careful  investigations,  have  come  to  the  conclusion  that 
the  thyroid  originated  only  from  a  single  median  evagination  taking 
place  in  the  anterior  wall  of  the  pharynx,  between  the  three  divisions 
of  the  tongue,  from  which  place  it  descends  into  the  neck  to  its  resting 
place  astride  the  upper  portion  of  the  trachea. 

On  a  frontal  and  vertical  cut  the  human  embryo,  two  weeks  old, 
shows  laterally  of  the  cephalic  extremity  a  series  of  branchial  arches 
separated  by  branchial  grooves.  In  the  human  embryo  of  6  months  five 
branchial  grooves  are  present,  the  fourth  being  divided  into  two. 
Between  the  second,  third,  fourth,  and  fifth  branchial  arches  on  both 
sides,  and  between  the  inferior  maxillary  and  the  basis  of  the  heart,  there 
is  a  triangular  space  which  is  called  the  mesobranchial  field  of  His 
(Fig.  7).  From  this  field  will  derive  the  thyroglossus  duct  and  the  thy- 
roid gland.  Laterallv  of  the  mesobranchial  field  of  His  are  found 
branchial  arches  and  branchial  grooves  which  altogether  form  the  branchial 
apparatus.  Branchial  arches  and  branchial  grooves  are  separated,  one 
from  the  other,  by  a  thin  wall  of  tissue  covered  inside  with  endoderm 
and  outside  with  ectoderm.  These  branchial  and  mesobranchial  elements 
give  rise  to  very  difFerent  and  very  important  organs  and  to  very  well- 
differentiated  embryonic  residues  from  which  thyroid  tumors  may 
derive;  therefore  from  an  embryological  point  of  view  it  seems  logical 
to  divide  the  tumors  of  the  thyroid  into  tumors  of  mesobranchial  origin 
and  tumors  of  branchial  origin. 

In  the  mesobranchial  field,  just  in  front  of  the  second  groove,  a 
median  invagination  of  the  walls  of  the  pharynx  appears,  forming  a 
depression  which  becomes  deeper  and  deeper,  and  finally  forms  the 
thyroglossus  duct.  At  its  lower  end  this  duct  bifurcates,  forming  two 
terminal  buds,  which  proliferate  into  a  glandular  organ  (Fig.  7)  which 
later  on  will  be  the  thyroid  gland. 

In  the  middle  of  the  second  month  of  intra-uterine  life  the  thyro- 


EMBRYOLOGY 


25 


glossus  duct  divides  into  two  portions,  the  superior  and  the  inferior. 
The  superior  portion,  called  the  lingual  duct,  extends  from  the  hyoid 
bone  to  the  foramen  cecum  of  the  tongue;  the  lower  portion,  or  thyroid 
duct,  extends  from  the  hyoid  bone  to  the  isthmus  of  the  thyroid  gland. 
This  division  of  the  thyroglossus  duct  into  the  lingual  and  thyroid 
ducts  is  produced  by  the  hyoid  bone,  which,  at  the  end  of  the  fifth  week, 
is    represented    by    a    cartilaginous    mass    interposed    between    the    two 


Fig.  7. —  1,  first  branchial  groove;  2,  second  branchial  groove;  3,  third  branchial 
groove;  4,  fourth  branchial  groove;  5,  fifth  branchial  groove;  A,  thymic  portion  of  the 
parathyroid;  ./',  thyroid  portion  of  the  parathyroid;  B,  thymus;  C,  postbranchial  bod)  ; 
'I'll,  thyroid. 


segments  of  the  thyroglossus  duct.  Sometimes  this  interposition  does 
not  take  place,  and  in  that  case  the  thyroglossus  duct  forms  a  continu- 
ous canal  extending  from  the  foramen  cecum  through  the  lingual  raphe, 
and  passing,  as  a  rule,  behind  and  sometimes  in  front  of  the  hyoid  bone. 
In  few  exceptions  it  passes  directly  through  the  body  oi  the  bone. 

Ordinarily,  the  thyroglossus  duct  bifurcates  in  front  of  the  larynx, 
forming  the  isthmus,  tin-  lobes  being  formed  by  tin-  two  terminal  buds. 


26 


ANATOMY  AXD  EMBRYOLOGY 


However,  the  bifurcation  of  the  thyroglossus  duct  may  take  place 
higher  up,  as  far  as  the  foramen  cecum;  in  that  case  we  shall  have  two 
pyramidal  processes,  one  on  each  side,  or  we  may  have  two  lobes  with 
the  pyramids,  but  no  isthmus  at  all  (Figs.  1-4). 

The  thyroglossus  duct  has  a  constant  and  specific  structure.  It  is 
lined  with  one  layer  of  cylindrical  epithelium  provided  in  places  with 
vibratile  cilia.  Very  rarely  is  this  duct  lined  with  pavimentous  epithe- 
lium. The  terminal  portion  of  the  thyroglossus,  which  constitutes  later 
on  the  thyroid  gland,  has  at  first  the  same  cylindrical  structure,  so  that 
at  the  end  of  the  fifth  or  sixth  embryonic  month  the  thyroid  is  formed 


•-\ 


mm 


.•■■•■•..-■ 


*zzm 


'■*"+ 


Fig.  8. — Congenital  goiter.     Simple  parenchymatous  goiter  fotmed   by  a  cellular  mass 
not  yet  differentiated  into  adult  alveoli.      X  58. 


by  alveoli  lined  with  one  single  layer  of  epithelium;  their  lumen  is  very 
small  and  does  not  contain  colloid;  protoplasm  is  clear,  has  no  vacuoles; 
nuclei  are  compact  and  the  chromatin  forms  a  stain  instead  of  a  network. 
Later  on  this  epithelium  loses  its  cylindrical  character,  and  at  the 
end  of  the  seventh  month  the  structure  of  the  thyroid  gland  has  changed 
considerably;  an  intense  cellular  desquamation  takes  place  and  fills 
the  lumen  of  the  alveoli,  so  that  toward  the  end  of  the  intra-uterine  life 
the  thyroid  is  composed  of  a  uniform,  non-differentiated  mass  of  cells 
(Fig.  8)  pressed  one  against  the  other  and  containing  a  few  capillary 
vessels.      The   nuclei    are    large,    swollen,    clear;     no   colloid    is    present. 


EMBRYOLOGY  27 

The  cause  of  the  desquamation  is  yet  unexplained.  A  few  weeks  after 
birth,  however,  regeneration  of  the  thyroid  takes  place;  the  epithelium 
shapes  itself  into  epithelial  cords  which  undergo  a  process  of  direct 
division,  thus  forming  new  alveoli  in  which  the  epithelium  becomes 
cubic  or  flat. 

Consequently,  it  may  be  said  that  the  thyroid  passes  through  three 
different  stages: 

i.  The  embryonic  ox  thyroglossus  stage  formed  by  cylindrical  epithelium. 

2.  The.  fetal  stage  formed  by  a  non-differentiated  cellular  mass. 

3.  The  adult  or  vesicular  stage. 

The  embryonic  and  fetal  types  may  leave  persistent  inclusions  in 
the  thyroid.  Wolfler  has  demonstrated  that  these  inclusions  of  fetal 
parenchyma  are  not  seldom  found  in  the  thyroid,  and  that  they  may 
result  in  the  production  of  a  tumor  known  as  the  fetal  adenoma. 

After  the  thyroglossus  duct  has  formed  the  thyroid  gland  with  its 
lobes  and  isthmus  it  gradually  becomes  atrophied  and  forms  a  fibrous 
cord,  called  by  His  the  thyroglossus  tractus,  and  which  extends  from  the 
foramen  cecum  of  the  tongue  to  the  pyramidal  process.  Exceptionally, 
this  canal  may  remain  permeable  in  all  its  course  from  the  base  of  the 
tongue  to  the  thyroid. 

The  thyroglossus  duct  may  leave  over  its  entire  course  islands  of 
thyroid  tissue  at  the  cost  of  which,  later  on,  accessory  glands  or  goiters 
may  develop.  Sometimes  the  thyroglossus  tract  does  not  terminate  in 
the  thyroid  but  extends  downward  into  the  anterior  mediastinal  space, 
and  may  even  reach  the  aorta.  In  that  case  accessory  glands  may  be 
left  over  the  entire  length  of  this  course.  Thus  is  explained  the  origin 
of  accessory  thyroid  glands,  and  of  tumors  of  the  mesobranchial  type 
developed,  not  only  at  the  base  of  the  tongue  and  in  the  cervical  region, 
but  also  in  the  mediastinal  space. 

In  the  same  way  during  the  embryological  evolution  islands  of 
eetodermic  epithelium  may  be  left  behind,  remaining  in  close  contact 
with  the  thyroid  gland.  Later  on  these  inclusions  are  liable  to  give  rise 
to  tumors  with  pavimentous  epithelium,  hence  cancroid  of  the  thyroid. 

\  he  dorsal  cul-de-sac  of  the  third  branchial  groove  forms  the  external 
or  thymic  parathyroid.  The  ventral  portion  of  this  third  groove  forms 
the  internal  parathyroid.  The  ventral  cul-de-sac  of  the  fifth  branchial 
groove  forms  the  postbranchial  or  ultimobranchial  body. 

Postbranchial  Bodies.  -Van  Bemmemen  discovered  in  the  embryo  of 
the  shark  and  thornback,  behind  and  on  each  side-  of  the  last  branchial 
arch,  a  pocket-like  formation  containing  follicles,  and  resembling  the 
thyroid  gland.  This  glandular  organ  lies  so  near  the  heart  that  Van 
Bemmemen  called  it  supraparacardial  body.  With  the  exception  of  the 
cyclostoma  and  the  temeostiver  such  organs  have  been  tunnel  in  other 
classes  of    vertebrates,   for   instance  in    tin    amphibious   reptiles,   birds 


28 


ANATOMY  AND  EMBRYOLOGY 


and  mammalian  animals.  Because  these  organs  are  always  situated 
behind  the  last  branchial  arch,  Miwa  called  them  postbranchial  bodies 
(Fig.  7).  In  amphibious  reptiles,  birds  and  mammalian  animals  these 
postbranchial  bodies  give  rise  to  follicles  with  epithelium  and  vibratile 
cilia,  but  according  to  Miwa,  colloid  is  never  found. 

These  colloid  bodies  have  been  considered  by  a  few  authors  as  giving 
rise  to  the  lateral  thyroids,  which  after  fusion  with  the  median  thyroid 
were  thought  to  form  the  thyroid  gland.  But  this  has  been  disproved 
by  Miwa,  His,  Verdin  and  Tourneux.  In  their  opinion  these  post- 
branchial bodies  have  nothing  to  do  with  the  formation  of  the  thyroid 
gland.  They  are  separate  organs  whose  significance  is  not  yet  clear,  and 
which  in  Verdin's  judgment  undergo  an  atrophy  and  finally  disappear. 

From  an  embryological  stand-point,  De  Quervain,  Delore  and  Ala- 
martine  were  consequently  justified  in  classifying  the  thyroid  tumors  in 
two  large  classes: 

I.  Tumors  of  mesobranchial  origin. 
II.  Tumors  of  branchial  origin. 

Tumors  of  Mesobranchial  Origin. 

These  are  median  tumors  in  the  neck  which  originate  from  the 
thyroglossus  duct  and  from  the  organs  which  derive  from  it,  namely, 
the  thyroid  gland  and  the  accessory  thyroid  gland. 


1.    Tumors  of  ectodermic  origin  due  to  inclu- 
sion of  ectodermic  epithelium. 


Tumors  of  Branchial  Origin. 

All   cancers  with   pavimentous  epithelium. 


2.    Tumors  of  endodermic  origin  due  to  inclu- 
sion of  endodermic  epithelium. 


1.  From  the  thyroglossus  duct. 

2.  From  the  thyroid  itself. 

3.  From  the  accessory  thyroid  glands. 


a.  First   branchial   groove   gives  fistula    in 

connection  with  the  external  auditory 
canal  and  the  mixed  tumors  developed 
in  the  parotid  and  submaxillary 
glands. 

b.  Second  branchial  groove  gives  branchial 

cyst  and  fistula  and  all  mixed  tumors  of 
the  lateral  region  of  the  neck. 

c.  Dorsal  portion  of  the  third  and  fourth 

grooves  gives  parastruma. 

d.  Ventral    portion   of  the   fourth    or   fifth 

branchial  grooves  gives  the  post- 
branchial tumors. 

a.  Lingual  goiter. 

b.  Median,     congenital    cyst    and     fistula; 

benign  and  malignant. 

c.  Goiters  with  cylindrical  epithelium. 

a.  All  benign  goiters. 

b.  All  malignant  goiters. 

a.  All  benign  accessory  goiters. 

b.  All  malignant  accessory  goiters. 


EMBRYOLOGY  29 

This  synoptical  picture  based  on  embryological  considerations  is 
very  clear  and  scientific.  It  gives  the  key  to  the  explanation  of  these 
very  obscure  tumors  found  in  the  neck  and  in  the  thyroid  gland,  which 
have  so  long  been  a  puzzle  to  the  pathologist.  Easily  explained  thereby 
will  be  the  origin  of  lingual  goiter;  of  the  median  and  lateral  cvsts 
and  fistulae  of  the  neck;  of  the  accessory  glands  from  all  along  the  neck 
and  in  the  superior  portion  of  the  mediastinal  space.  Easily  explained, 
too,  are  these  puzzling  and  various  tumors  in  which  the  thyroid  is  so 
rich,  as  the  parastruma,  papilloma,  postbranchial,  mixed  tumors,  etc. 


CHAPTER   II. 
PHYSIOLOGY  OF  THE  THYROID. 

History. — Theories  regarding  the  physiology  of  the  thyroid  have 
been  numerous.  Wharton  thought  it  was  merely  a  cosmetic  organ  whose 
function  was  to  produce  a  nice,  soft,  roundness  of  the  neck.  Other 
authors  thought  that  it  acted  as  a  mechanical  support  to  the  larynx, 
and  protected  this  organ  against  cold.  Boerhaave  thought  that  it  acted 
as  a  cushion  whose  gentle  pressure  served  as  a  modulator  of  the  voice. 
Morgagni,  Santorini,  Winslow  and  Lalouette  thought  that  the  gland 
was  in  direct  communication  with  the  larynx,  and  that  it  probably  had 
an  excretory  canal  emptying  into  the  region  of  the  vocal  cords;  and 
that  under  such  conditions  the  secretion  of  the  thyroid  acted  as  a  lubri- 
cant for  these  cords.  As  late  as  1870  Ricou  believed  in  the  existence  of 
this  excretory  canal;  some  other  authors  believed  that  the  thyroid 
communicated  directly  with  the  esophagus  and  considered  the  foramen 
cecum  as  the  point  of  outlet  of  the  canal. 

For  quite  a  long  time  the  thyroid  was  considered  as  a  mechanical 
regulatory  organ  of  the  blood  circulation  and  was  regarded  as  an  arterial 
reservoir  intercalated  between  the  cephalic  and  the  caroticosubclavian 
systems;  filled  with  blood,  the  gland  was  thought  capable  of  compress- 
ing the  carotids,  thus  diminishing  the  quantity  of  blood  going  into  the 
brain.  Compared  to  a  sponge  capable  of  derivating  or  giving  up  at 
will  the  blood  destined  to  the  cerebral  organs,  the  thyroid  was  then 
regarded  as  a  safety-vent  for  the  cerebral  circulation.  There  is  no  need 
to  say  that  these  hypotheses  are  for  the  most  part  purely  fanciful  and 
are  not  supported  by  any  experimental  facts.  However,  it  might  be 
incorrect  to  claim  that  the  thyroid  has  no  effect  whatsoever  on  the 
cerebral  circulation,  as  this  gland  receives  its  nerve  supply  from  the 
superior  laryngeal  nerve  containing  the  vasodilatator^  fibers,  and  from 
the  sympathetic  nerve  which  contains  the  vasoconstrictory  fibers. 
Experimentation  shows  that  excitation  of  the  central  end  of  the  superior 
laryngeal  nerve  causes  an  intense  reflex  vasodilatation  of  the  thyroid: 
hence  diminution  of  the  quantity  of  blood  directed  toward  the  cere- 
brum; on  the  other  hand,  irritation  of  the  sympathetic  nerve  causes  a 
vasoconstriction,  and  consequently  an  increase  of  the  quantity  of  blood 
thrown  into  the  cerebral  circulation.  It  is  therefore  possible  that  in 
certain   given  conditions   this   mechanism  is  called   into  play  and   thus 


RESULTS  OF  EXPERIMENTAL   THYROIDECTOMY  31 

mav  be  regarded  to  a  certain  extent  as  a  regulator  of  the  cerebral 
circulation. 

One  of  the  most  curious  theories  of  the  physiology  of  the  thyroid  is 
that  of  Fomens.  According  to  this  author  this  organ  plays  an  important 
part  in  the  physiology  of  sleep;  it  swells  up  during  sleep  because  it 
retains  a  certain  portion  of  the  blood  destined  to  the  brain  and  gives  it 
off  again  during  the  period  of  wakefulness.  Evidently  this  author 
believes  that  sleep  is  due  to  cerebral  anemia. 

In  conclusion  we  may  say  that  the  regulation  theory  is  not  sup- 
ported by  any  experimental  facts  nor  by  surgical  experience,  as  no  dis- 
turbances in  the  cerebral  circulation  are  noticed  after  operations.  The 
histological  structure  of  the  gland,  too,  speaks  against  this  theorv;  the 
thyroid  is  a  glandular  and  not  a  cavernous  organ. 

All  these  theories  have  only  an  historical  interest.  Our  knowledge 
of  the  physiological  function,  although  still  incomplete,  has  become 
more  precise  in  the  last  quarter  of  a  century;  the  thyroid  must  be 
regarded  as  a  glandular  organ  of  great  importance  in  metabolism. 

In  1840  Astley  Cooper  noticed  that  thyroidectomy  in  animals  was 
followed  by  a  peculiar  symptom-complex,  but  he  did  not  pursue  his 
experiences  any  further  nor  did  he  give  his  observations  their  correct 
interpretation.  In  1859  Schiff  called  attention  to  the  dangers  connected 
with  thyroid  insufficiency.  His  experimental  results,  however,  passed 
unnoticed  until  1883,  when  Kocher  and  Reverdin  made  their  epoch- 
making  discovery. 

The  physiology  of  the  thyroid  may  be  studied  from  two  angles. 
\  aluable  information  may  be  gained  by  performing  a  complete  thy- 
roidectomy in  animals  to  see  what  the  outcome  will  be.  Information 
may  be,  furthermore,  secured  by  studying  the  influence  of  the  adminis- 
tration of  the  gland  itself  upon  the  different  organs  and  functions  of  the 
body. 

Results  of  Experimental  Thyroidectomy. — The  thvroid  is  an  organ 
necessary  to  life  and  its  absence  produces  a  clinical  syndrome  which  has 
been  called  myxedema  or  cachexia  thyreopriva,  and  which  terminates,  as 
a  rule,  in  death.  Schiff,  Wagner,  Horsley,  von  Eiselsberg  and  others 
have  shown  that  extirpation  of  the  thyroid  in  young  animals  causes 
death  much  sooner  than  extirpation  in  adults.  Children  with  total 
aplasv  of  the  thyroid  never  reach  puberty.  The  most  important  symp- 
toms observed  after  complete  thyroidectomy  are  a  retarded  metabolism 
and  an  arrest  in  the  growth  of  the  osseous  system,  myxedematous 
infiltration  of  the  skin  and  intellectual  disturbances. 

In  young  animals  the  arrest  of  development  is  considerable  and 
affects  at  the  same  time  the  skeleton,  the  nervous  system,  and  the  gen- 
ital apparatus.     Young   thyroidectomized   animals  remain  small;   their 


32  PHYSIOLOGY  OF  THE  THYROID 

bones  do  not  develop;  their  cartilages  and  epiphyses  do  not  proliferate; 
they  retain,  in  fact,  their  fetal  aspect.  The  skin  becomes  rough  and 
infiltrated  with  a  mucinoid  substance,  hence  the  name  myxedema.  This 
mucinoid  infiltration  is  found,  too,  in  muscles,  nerves,  and  other  organs. 
The  young  animals  remain  apathetic  and  dejected;  their  movements 
are  slow  and  awkward,  while  physical  activity  is  a  burden  to  them. 
The  genital  organs  remain  infantile;  the  testicles  do  not  descend  and, 
as  a  rule,  do  not  secrete  spermatozoids;  the  ovaries  remain  small  and 
become  sclerocystic.  Furthermore,  the  respiratory  exchanges  and  oxi- 
dation processes  are  diminished;  the  animals  become  anemic;  their 
temperature  is  low  and  the  development  of  the  disease  is  progressive 
until  death  occurs. 

A  complete  thyroidectomy  in  adult  animals  produces  the  same 
clinical  picture  but  less  intensified.  The  muscular  system  becomes 
weak  and  paretic;  the  nervous  and  psychic  functions  are  disturbed;  the 
skin  becomes  swollen  and  edematous,  while  the  hair  becomes  dry  and 
brittle.  The  metabolism  is  diminished,  but  as  these  animals  have 
reached  normal  growth  no  disturbances  of  the  osseous  system  are  found. 

Food  seems  to  have  a  certain  influence  on  the  severity  of  the  develop- 
ment of  myxedematous  conditions.  Thyroidectomized  dogs,  for  instance, 
seem  to  stand  a  cooked-meat  diet  with  impunity,  but  as  soon  as  they 
are  given  fresh  meat  the  symptoms  of  thyroid  insufficiency  at  once 
become  more  severe.  Death  can  be  delayed  for  a  longer  period  if  the 
animals  are  kept  on  a  milk  diet.  Apparently,  thyroidectomized  animals 
are  unable  to  destroy  certain  toxic  products  of  a  meat  diet. 

After  the  thyroid  has  been  completely  removed  its  functional  insuffi- 
ciency becomes  manifest  more  or  less  rapidly,  sometimes  in  a  few  days, 
sometimes  after  a  few  weeks,  and  sometimes  after  many  months. 

Tizzoni,  Alonzo  and  Ughetti  did  not  observe  symptoms  before  nine 
months,  and  Horsley  waited  one  and  three-quarters  years  before  symp- 
toms of  cachexia  appeared  in  a  sheep  which  had  been  completely  thy- 
roidectomized. This  will  explain  why  there  have  been  authors  claiming 
that  thyroidectomy  had  no  efFect  upon  the  condition  of  the  animals. 
Either  these  authors  did  not  wait  long  enough  for  myxedematous  symp- 
toms to  appear  or  they  mistook  the  lymphatics  or  submaxillary  glands 
for  the  thyroid,  or  if  they  did  remove  the  thyroid,  their  operation  was 
not  complete,  or  if  it  was,  accessory  thyroids  must  have  been  present. 

Thyroid  and  Parathyroids. — For  a  long  time  great  confusion  has  pre- 
vailed concerning  the  correct  interpretation  of  phenomena  observed 
after  thyroidectomy,  as  symptoms  depending  solely  upon  thyroid  insuf- 
ficiency were  ascribed  to  parathyroid  disturbances,  and  vice  versa.  It 
was  thought,  too,  that  the  consequences  of  thyroidectomy  were  more 
severe  in  certain  species  of  animals  than  in  others.     Horsley,  in  1891, 


THYROID  AXD  PARATHYROIDS  33 

summing  up  the  results  of  experimental  pathology,  found  that  thyroid- 
ectomy was  not  followed  by  cachexia  in  birds  and  rodents,  that  it  took 
a  mild  course  in  ruminants,  and  that  it  was  of  the  utmost  severity  in 
carnivorous  animals.  To  be  sure,  everything  being  equal,  symptoms 
following  total  thyroidectomy  in  carnivorous  animals  are  more  severe 
than  in  herbivorous  animals,  because,  as  we  have  seen,  a  meat  diet 
seems  to  cause  more  symptoms  than  a  milk  or  herbivorous  diet,  but  this 
is  not  the  sense  of  the  above  statement.  Horslev  meant  that  carniv- 
orous animals  became  acutely  sick  and  died  after  a  few  days  in  the  most 
acute  convulsions,  whereas  herbivorous  animals  stood  the  operation 
more  easily  and  developed  gradually  a  chronic  pathological  condition 
known  as  myxedema.  As  we  see,  he  did  not  at  the  time  separate  the 
svmptoms  belonging  to  thyroid  insufficiency  from  the  ones  of  para- 
thyroid origin. 

Thyroid  and  parathyroids  are  not  only  anatomically  and  pathologi- 
cally different,  but  their  physiological  function  is  likewise  not  similar. 
If  in  animals  the  thyroid  alone  is  removed  and  the  parathyroids  left 
in  situ,  a  chronic,  slow  cachexia,  which  we  call  myxedema,  takes  place; 
but  if  the  parathyroids  alone  are  removed  and  the  thyroid  left  in  situ, 
the  most  severe  convulsions  appear  very  soon  and  the  animal  dies  of 
tetany  in  the  course  of  a  few  days.  Now,  then,  the  error  made  in  the 
interpretation  of  these  symptoms  can  be  very  easily  explained.  In 
carnivorous  animals  the  parathyroids  are  found,  as  a  rule,  embedded 
within  the  capsule  in  the  thyroid  tissue  itself,  while  in  herbivorous 
animals  the  parathyroids  are  located  outside  the  capsule  of  the  gland. 
In  sheep  and  goats,  for  instance,  a  considerable  amount  of  parathyroid 
tissue  is  present  outside  of  the  thyroid  gland;  in  rabbits  two  of  the 
parathyroids  have  no  relation  whatsoever  with  the  thyroid:  conse- 
quently, when  thyroidectomy  in  carnivorous  animals  was  perfornu-d. 
the  parathyroids  were  removed  ipso  facto  at  the  same  time,  whereas  in 
herbivorous  animals  they  were  left  uninjured;  hence  the  difference  in 
tin  clinical  picture  in  both  species  of  animals.  In  one  case  they  devel- 
oped tetany,  in  the  other  myxedema. 

Pineles,  on  the  strength  of  his  clinical  material  on  the  congenital 
absence  of  the  thyroid,  had  already  come  to  the  conclusion  that  the 
parathyroids  and  thyroid  were  two  entirely  different  organs,  anatomi- 
cally as  well  as  functionally.  In  his  judgment,  if  nature  wanted  to 
undertake  an  experiment  to  demonstrate  the  independence  of  the  para- 
thyroid system  from  the  thyroid  one,  it  could  not  have  done  it  more 
elegantly  and  more  fully  than  in  thyroid  aplasy.  We  know  that  in  such 
condition  the  thyroid  is  entirely  absent,  but  the  parathyroids  are  pre- 
served. In  X  out  of  14  cases  of  thyroid  aplasy  he  was  able  to  demon- 
strate microscopically  the  absence  of  the  thyroid  and  the  presence  of 
3 


34  PHYSIOLOGY  OF  THE  THYROID 

normal  parathyroids.  Furthermore,  he  showed  that  in  4  cases  of  lingual 
goiter  which  had  been  operated,  myxedema  followed,  whereas  no  symp- 
toms of  tetany  were  observed,  and  for  the  simple  reason  that  in  such 
cases  every  bit  of  thyroid  tissue  had  been  removed,  but  the  parathy- 
roids had  remained  untouched. 

To  Gley,  Vassale  and  Generali,  however,  belongs  the  credit  for  hav- 
ing demonstrated  beyond  doubt  that  the  symptoms  observed  in  animals 
after  strumectomy  did  not  all  recognize  the  same  origin,  and  that  ner- 
vous symptoms  and  convulsions  were  due  to  an  injury  of  the  parathy- 
roids, whereas  myxedema  recognized  as  its  cause  a  thyroid  insufficiency. 
Since  then  these  conclusions  have  been  investigated  and  controlled  by  a 
great  number  of  authors  and  found  correct.  We  can  today  safely  con- 
clude that  the  thyroid  and  parathyroids  are  two  entirely  different 
organs,  and  that  to  the  insufficiency  of  one  organ  belongs  a  set  of  symp- 
toms which  differ  entirely  from  the  clinical  picture  due  to  insufficiency 
of  the  other  one.  Such  conclusions  are  based  upon  the  following  rea- 
sons: After  partial  extirpation  of  the  parathyroids,  tetany  does  not 
occur;  no  lesions  of  the  nerves  in  the  neck,  as  extensive  and  compli- 
cated as  they  may  be,  can  determine  similar  symptoms;  furthermore, 
histologically,  the  parathyroids  are  different  from  the  thyroid.  If  the 
thyroid  alone  is  removed,  no  tetanic  convulsions  develop,  but  myxedema 
follows;  if  the  parathyroids  are  removed  and  the  thyroid  is  left 
untouched,  the  clinical  picture  of  parathyroid  insufficiency  at  once 
becomes  acute,  but  no  myxedema  follows.  The  trophic  disturbances  are 
due  to  the  absence  of  the  thyroid  alone,  whereas  the  acute,  convulsive 
troubles  must  be  referred  to  the  suppression  of  the  parathyroid  func- 
tion. Furthermore,  in  athyroidism,  the  thyroid  function  alone  is  sup- 
pressed, whereas  the  parathyroids  remain  normal.  In  postmortems  of 
myxedematous  patients  and  cretins  where  no  vestige  of  the  thyroid 
could  be  found  the  parathyroids  were  found  normal.  Finally,  para- 
thyroid opotherapy  is  often  capable  of  curing  tetany,  whereas  thyroid 
opotherapy  is  inefficacious. 

I  know  that  on  the  strength  of  certain  experiments  made  by  Gley 
in  1909-1911,  by  A.  E.  Melnikov  in  1909,  by  Iselin  in  191 1  (who  found 
that  young  parathyroidectomized  animals  which  did  not  succumb  to 
tetany  developed  a  condition  similar  to  rickets  and  died  of  cachexia),  by 
Louis  Morel  in  191 1  (who  seems  to  have  demonstrated  that  after  para- 
thyroid extirpation  symptoms  of  slow  cachexia  similar  to  the  one  seen 
in  myxedema  develop),  Gley,  in  the  last  edition  of  his  Physiology,  191 3, 
believes  there  must  exist  a  functional  association  between  these  two 
organs.  According  to  these  authors  tetany  is  not  the  only  consequence 
of  the  parathyroid  insufficiency,  but  the  suppression  of  these  glandules 
determines  cachexia  and  trophic  disturbances  of  the  skeleton,  probably 


POSTOPERATIVE  TETANY  IN  ANIMALS  35 

by  disturbing  the  entire  chemical  metabolism.  How?  It  is  not  known. 
Swale,  Vincent  and  Joly  do  not  want  to  admit  that  the  parathyroids 
have  a  specific  function  of  their  own.  The)'  believe  that  the  thyroid 
and  the  parathyroids  form  a  unique,  physiological  system,  that  the  thy- 
roid is  capable  of  a  vicarious  function  in  case  of  parathyroid  insufficiency, 
and  vice  versa.  In  view  of  the  enormous  amount  of  work  done  in  that 
line  by  the  most  competent  observers  such  conclusions  seem  audacious 
and  presumptuous.  They  seem  certainly  contradicted  by  the  clinical 
facts. 

Postoperative  Tetany  in  Animals. — The  symptoms  due  to  complete 
parathyroidectomy  develop  soon  after  operation  and  are  rapidly  fatal. 
Localized  or  generalized  tetany  is  the  dominant  symptom.  A  few  hours 
or  a  day  or  two  after  parathyroidectomy  has  been  performed,  symptoms 
begin;  the  gait  of  the  animal  becomes  unsteady  and  awkward;  an  intense 
tremor  develops  and  later  on  clonic  muscular  contractions,  tetanic 
cramps,  resembling  the  contractions  seen  in  tetanus,  dominate  the  pic- 
ture. Resting  apparently  quietly  for  a  time  the  animal  is  suddenly 
taken  with  a  convulsive  spell,  falls  on  his  side,  with  teeth  chattering; 
rigidity  may  or  may  not  be  present;  a  fewr  minutes  after  everything  is 
over.  These  spells  gradually  recur  more  frequently  and  the  spasmodic 
contractions  become  more  intensely  developed.  During  the  convulsions 
the  animal  cries,  showing  that  he  suffers;  his  hind  legs  are  contracted  and 
stiff  and  in  the  most  severe  cases  the  animal  may  lose  consciousness  for 
hours.  During  the  spell  his  temperature  rises  verv  high  and  may  reach 
109-uo0.  Respiration  is  accelerated.  During  the  spells  dyspnea  is 
very  marked,  tachycardia  is  present;  urine  is  scarce  and  often  contains 
albumin.  The  number  of  red  corpuscles  is  diminished,  whereas  the 
pol\  nuclears  are  increased.  Death  occurs,  as  a  rule,  five  to  eight  days 
after  parathyroidectomy,  and  takes  place  during  convulsions  or  coma. 

If  one  parathyroid  has  been  left  in  situ,  tetany  does  not  follow  or 
may  appear  only  temporarily.  This  is  so  true  that  Halstead  was  able 
in  a  very  elegant  and  conclusive  experiment  to  show  that  the  removal  of 
the  tour  parathyroids  in  an  animal  was  absolutely  harmless,  provided 
that  one  of  these  glandules  was  transplanted  into  the  abdominal  wall. 
I  he  animal  lived  without  showing  any  pathological  manifestations  what- 
ever. Hut  as  soon  as  the  transplanted  parathyroid  was  removed,  marked 
symptoms  of  tetany  soon  appeared  and  death  followed  quickly.  In 
some  instances  tetanv  developed,  although  one  parathyroid  had  been 
left  in  situ.  This  was  probably  due  to  the  fact  that  the  little  glandule 
had  been  unduly  traumatized  or  disturbed  and  had  gradually  under- 
gone resorption.  If  removal  of  the  parathyroids  is  done  gradually  and 
at  different  periods  of  time,  as  soon  as  the  whole  parathyroid  system  is 
removed,  the  symptoms  become  just  as  acute  as  if  all  the  pat  a  tin  roids 


36  PHYSIOLOGY  OF  THE  THYROID 

had  been  suppressed  in  one  sitting.  Although  the  symptoms  are  less 
marked  in  adults  than  in  young  animals,  the  termination  is  neverthe- 
less fatal  in  both.  It  is  during  pregnancy  that  parathyroid  insufficiency 
presents  its  maximum  of  development.  Adler  and  Thaler  have  shown 
experimentally  that  the  removal  of  a  small  portion  of  the  parathyroids 
in  pregnant  animals  caused  severe  symptoms  of  hypoparathyroidism, 
whereas  the  removal  of  the  same  amount  of  parathyroid  tissue  in  non- 
pregnant animals  was  without  effect. 

Iselin  showed  that  the  offspring  of  rats  which  had  undergone  experi- 
mental lesions  of  the  parathyroids  showed  a  marked  congenital  tendency 
to  tetany.  This  latent  parathyroid  insufficiency  was  so  marked  that 
the  removal  of  one  parathyroid  only  was  sufficient  to  determine  the 
most  violent  tetany,  and  which  always  proved  fatal. 

Pfeiffer  and  Mayer  found  in  the  blood  of  dogs  suffering  from  post- 
operative tetany  a  toxic  principle  which  injected  into  mice  did  not  cause 
any  disturbance  whatever  until  the  parathyroids  of  these  mice  had  been 
subjected  to  trauma.  In  that  case,  even  if  a  large  portion  of  the  para- 
thyroids were  left  uninjured,  the  mice  developed  the  most  severe  tetanic 
symptoms,  whereas  the  controls  remained  unaffected. 

Action  of  Thyroid  Administration  and  Thyroidectomy  on  Metabolism. — ■ 
Under  normal  conditions  the  thyroid  secretion  is  a  physiological  product 
playing  a  very  important  part  in  metabolism,  and  elaborated  in  suffi- 
cient quantities  to  meet  the  physiological  demands  of  the  organism, 
but  as  soon  as  it  is  secreted  in  excessive  or  insufficient  amount,  marked 
pathological  symptoms  follow;  hence,  hyperthyroidism  and  hypothy- 
roidism. 

From  the  beginning  of  opotherapy  it  has  been  observed  that  if  thy- 
roid preparations  are  given  to  animals  or  human  beings,  a  certain  train 
of  toxic  symptoms  which  we  call  acute  thyroidism  may  sometimes  follow, 
as  tachycardia,  headache,  vertigo,  mental  excitation,  tremor,  nausea, 
vomiting,  polyuria,  albuminuria,  glycosuria,  and  moderate  exophthal- 
mos. The  symptoms  observed  in  such  conditions  are  of  two  varieties: 
(i)  the  ones  due  to  the  physiological  properties  of  the  thyroid  itself; 
(2)  the  ones  due  to  adulterated  thyroids.  This  latter  condition  will  be 
discussed  in  the  chapter  on  Opotherapy. 

Some  of  the  symptoms  found  in  acute  thyroidism  are  very  similar 
to  those  found  in  iodin  intoxication,  as  cerebral  excitation,  palpitations, 
tremor,  etc.  Ewald  believes  that  a  certain  number  of  symptoms  seen 
in  acute  thyroidism  may  be  due  to  the  excessive  or  rapid  phenomena 
of  disassimilation  and  to  the  direct  action  of  the  drug  on  the  nervous 
centers.  Thyroid  extract  injected  into  normal  animals  produces  at 
first  prostration  and  somnolence,  and  soon  after  tachycardia,  tremor, 
fever,  dyspnea,  extreme  agitation,  brilliancy  of  the  eyes,  slight  exoph- 


ACTION  OF  THYROID  OX  THE  CARDIOVASCULAR  SYSTEM     37 

thalmos,  and  polyuria.  Gradually  the  animals  lose  flesh,  have  diarrhea, 
melena,  polyuria,  albumin,  and  finally  sink  into  a  state  of  stupor,  become 
semiparalyzed  in  their  hind  legs,  and  die.  Young  animals  succumb 
very  much  sooner  to  hyperthyroidization  than  adult  ones.  Ballet  saw 
a  young  dog,  five  or  six  months  old,  die  seven  days  after  daily  intra- 
venous injections,  whereas  adult  animals  could  stand  doses  three  times 
larger  for  months. 

In  certain  instances,  thyroid  extract  being  used  in  subcutaneous 
injections,  the  same  authors  could  witness  the  development  of  a  real, 
experimental  goiter.  Lanz  and  Trachewski  were  able  to  produce  an 
atrophic  thyroiditis  with  thyroid  feeding.  Canter  even  saw  the  develop- 
ment of  a  myxedema. 

Injected  subcutaneously,  intravenously,  or  given  by  mouth,  thy- 
roid extracts  have  more  or  less  the  same  influence  on  previously  thyroidec- 
tomized  animals.  Trophic  disturbances  gradually  diminish;  myxedema 
becomes  less  marked;  the  skeleton  grows  again;  the  metabolic  exchanges 
increase;  blood  becomes  normal;  urine  is  secreted  in  greater  quantities, 
and,  in  short,  the  animals  have  a  tendency  to  become  normal  again. 

Action  of  the  Thyroid  on  the  Cardiovascular  System. — In  1895  Schoefer 
saw  that  an  intravenous  injection  of  thyroid  extract  lowers  the  blood- 
pressure  and  causes  a  marked  dilatation  of  the  peripheric  bloodvessels. 
As  this  has  been  found  correct  by  many  authors  since,  the  thyroid 
gland  has  been  regarded  as  an  organ  producing  vascular  hypotension. 
The  theories  set  forth  to  explain  this  physiological  phenomenon  have 
been  various.  Von  Cyon  sought  to  explain  it  by  the  "depressor  nerve 
theory."  In  collaboration  with  Ludwig  he  found  in  the  cervical  region 
of  the  rabbit  a  small  nerve  formed  by  the  junction  of  a  sympathetic 
branch  and  a  small  fillet  coming  from  the  superior  laryngeal  nerve 
which,  as  we  all  know,  is  a  branch  of  the  vagus  nerve.  This  nerve  is 
called  the  "depressor  nerve."  It  extends  downward  into  the  thoracic 
cavity,  reaches  the  heart,  and  terminates  in  the  endocardium  of  the 
ventricles  and  auricles  and  in  the  region  of  the  pulmonary  artery  and 
aorta.  Its  fibers  are  centripetal;  excitation  of  the  peripheric  end  does 
not  produce  any  effect,  but  irritation  of  the  central  end  is  painful  and 
determines  at  once  a  fall  in  the  blood-pressure,  which  is  caused  by  a 
reflex  dilatation  of  the  abdominal  vessels.  At  the  same  tune  the  heart 
action  becomes  retarded.  If  the  two  vagi  have  been  cut,  the  excitation 
of  the  depressor  nerve  has  no  more  influence  over  the  heart  action,  but 
produces,  just  the  same,  a  fall  in  the  blood-pressure.  According  t<>  its 
discoverer  the  function  of  the  depressor  nerve  is  to  protect  the  heart 
against  a  sudden  increase  of  pressure  in  the  aorta  and  pulmonary  artery. 
As  soon  as  the  blood-pressure  exceeds  certain  limits  tin  depressoi  fibers, 
terminating  in   the  endocardium,  transmit  at  once  the  irritation   to  the 


38  PHYSIOLOGY  OF  THE  THYROID 

centers  of  the  splanchnic  nerves,  either  inhibiting  the  vasoconstrictor 
centers  or  intervening  directly  on  the  vasodilatators  centers.  This 
causes  at  once  a  vasodilatation  of  the  abdominal  system.  On  account 
of  the  enormous  capacity  of  this  system  the  blood  is  deflected  from  the 
heart  and  consequently  the  blood-pressure  on  that  organ  becomes 
reduced,  hence  the  name  depressor  given  to  that  nerve;  at  the  same  time 
the  cardiac  action  becomes  slower.  "Therefore,"  says  von  Cyon,  "the 
depressor  nerve  should  be  regarded  as  a  means  of  defense  of  the  heart." 

At  the  same  time,  through  its  vagal  portion,  the  depressor  nerve 
puts  the  heart  and  the  thyroid  gland  in  direct  communication,  so  that 
a  mutual  and  direct  influence  of  one  organ  upon  the  other  is  established. 
Furthermore,  it  seems  to  be  an  accepted  fact  that  iodothyrin  and  thyro- 
globulin  increase  the  excitability  of  the  vagus  and  depressor  nerves, 
whereas  they  diminish  the  excitability  of  the  cardiac  accelerators. 
There  seems  to  be  no  doubt  in  von  Cyon's  mind  that  this  fall  in  blood- 
pressure  takes  place  through  the  depressor  nerve. 

According  to  Carnot  and  Georgiewski  the  fall  in  blood-pressure  can- 
not be  the  consequence  of  the  bulbar  or  spinal  paralysis  of  the  vaso- 
constrictor centers,  as  it  takes  place  after  the  bulb  and  medulla  oblon- 
gata have  been  destroyed.  Neither  can  it  be  a  question  of  paralysis  of 
the  peripheric  abdominal  vasoconstrictor  centers,  as  it  takes  place  after 
ligature  of  the  abdominal  organs.  The  fall  of  pressure  subsists  after 
both  vagi  have  been  paralyzed  with  atropin.  Very  likely,  according  to 
these  authors,  it  is  due  to  direct  action  of  the  thyroid  secretion  on  the 
cardiac  musculature. 

More  recently  Fiirth,  Schwarth,  Gautrelet  and  Lohmann  have 
thought  that  the  hypotensive  action  of  the  gland  was  due  to  choline. 
This  substance,  however,  is  not  found  only  in  the  thyroid  but  also  in 
all  the  other  organs.  Lohmann  found  in  the  thyroid  three  substances; 
one  which  he  called  arginine,  without  action  on  the  pressure;  another 
which  he  called  histinine,  markedly  hypertensive;  and  another  decidedly 
hypotensive. 

The  action  of  the  thyroid  secretion  on  the  heart,  according  to  Hask- 
ovec  and  others,  causes  a  marked  tachycardia,  increasing  with  the  slight- 
est effort.  This  marked  acceleration  persists  even  if  both  vagi  nerves 
have  been  cut.  The  frequency  of  cardiac  trouble  in  goiterous  patients 
is  well  known,  and  will  be  discussed  at  length  in  the  chapter  on  Goiter 
Heart. 

Action  on  the  Blood. — Soon  after  complete  thyroidectomy  in  animals 
a  marked  anemia  is  found;  the  red  corpuscles  diminish  and  a  leuko- 
cytosis takes  place.  It  was  on  account  of  this  anemic  condition  that 
the  thyroid  was  for  a  long  time  considered  as  a  hematopoietic  organ. 
After  thyroidectomy  the  blood  becomes  intensely  "venous,"  and  accord- 


ACTION  OX   THE  XUTRITIOX  39 

ing  to  Albertoni  and  Tizzoni,  in  the  most  severe  cases  of  thyroid  insuffi- 
ciency, the  amount  of  oxygen  may  sink  below  the  half  of  the  normal 
quantity;  of  course  the  amount  of  CO2  is  greatly  increased.  It  is  to 
this  venosity  of  the  blood  that  Herzen,  Vassale  and  Rogowitsch  attrib- 
ute the  increased  number  of  respirations  of  thyroidectomized  animals. 
Vassale  thinks  that  the  red  corpuscles  have  lost  their  capacity  for  fix- 
ing oxygen  because  he  found  that  soon  after  intravenous  injection  of 
thyroid  extract  the  blood  loses  its  venous  properties  and  becomes  normal 
again.  This  "anoxyhemy"  may  explain  why  thyroidectomized  animals 
are  so  sensitive  to  slight  changes  in  temperature.  This  is  true,  too,  of 
patients  suffering  from  cachexia  strumipriva  or  of  a  mild  degree  of 
spontaneous  hypothyroidism.  We  know  that  such  patients  prefer  to  be 
in  warm  rooms,  and  that  even  in  the  hottest  day  of  summer  they  do 
not  suffer  from  the  heat. 

The  number  of  red  corpuscles  is  materially  diminished  and  so  is  the 
hemoglobin;  polvnucleated  erythrocytes  are  not  a  rare  feature.  In 
such  conditions  the  red  corpuscles  have  a  fetal  aspect,  are  larger  in 
diameter,  and  contain  several  nuclei.  In  hyperthyroidism  the  red  cor- 
puscles do  not  show  any  modification  in  quality  nor  in  quantity.  Soon 
after  thyroidectomy  the  leukocytes  increase  in  number  but  diminish 
later  on.  In  hyperthyroidism  the  number  of  leukocytes  is  reduced,  but 
hvperlymphocytosis  combined  with  hypopolynucleosis  is  present. 

The  blood  serum  of  thyroidectomized  animals  possesses  toxic  prop- 
erties, and  according  to  Bianchi,  Jacobi  and  Wassermann  its  bactericide 
power  is  diminished.  This  explains  why  insufficiency  of  the  thyroid 
predisposes  to  infections.  Pagenoff  thinks  that  the  toxicity  of  the 
serum  is  caused  by  a  leukomain  which  probably  is  nothing  more  than 
the  thyreoproteid  of  Notkine. 

Action  on  the  Nutrition.  -After  thyroidectomy  the  nutritional  dis- 
turbances are  very  marked.  The  animal's  metabolism  is  reduced,  the 
nitrogenous  excretion  is  diminished,  and  in  the  skin  a  myxedematous 
infiltration  takes  place;  this  edema  is  hard,  does  not  pit  on  pressure, 
and  is  of  a  sallow  color.  According  to  Virchow  this  infiltration  is  caused 
by  an  active  proliferation  of  the  subcutaneous  tissue  and  to  the  pres- 
ence of  mucine.  In  myxedema  Horsley  has  found  mucine  not  only  in 
the  skin  but  in  the  blood,  muscles,  carotids,  etc.  He  considers  the 
thyroid  as  an  organ  regulating  the  assimilations  and  disassimilations; 
in  his  judgment,  after  removal  of  the  thyroid  these  assimilatory  pro- 
cesses do  not  take  place  any  more,  consequently,  albuminates  remain  in 
their  mucinoid  state  and  are  not  metabolized. 

The  thyroid  regulates  the  accumulation  and  repartition  <>l  fat  in  the 
body.  It  is  well  known  that  in  hypothyroidism  adipose  tissue  is 
increased,  whereas  in  hyperthyroidism  it  is  diminished.     Lately  it   has 


40  PHYSIOLOGY  OF  THE  THYROID 

been  demonstrated  that  the  thyroid  contains  a  lipase  which  in  thyroid 
insufficiency  is  diminished,  but  is  materially  increased  in  hyperthy- 
roidism, hence  the  intense  lipolytic  properties  of  the  serum  in  Graves' 
disease.  This  lipolytic  property  is  found  not  only  in  vivo  but  in  vitro, 
as  Youchtchenko  has  demonstrated. 

Action  on  the  Osseous  System. — Trophic  disturbances  of  the  osseous 
system  after  total  thyroidectomy  are  so  much  the  more  marked  that 
the  loss  of  thyroid  function  occurs  in  young  individuals.  The  growth 
of  skeleton  ceases,  bones  remain  short  and  fragile,  calcification  is  incom- 
plete, and  ossification  of  the  cartilages  is  arrested.  Bones  of  thyroid- 
ectomized  animals  compared  with  those  of  controls  are  seen  to  be  at 
least  a  third  smaller.  As  pointed  out  by  Gauthier,  the  fact  that  certain 
fractures  do  not  repair  normally  and  that  the  callus  formation  is  retarded 
for  weeks  and  months  may  be  recognized  as  the  result  of  thyroid  insuffi- 
ciency. Thyroid  opotherapy  in  certain  of  these  conditions  has  proved, 
indeed,  very  successful.  On  the  other  hand,  according  to  Holmgren 
individuals  affected  with  exophthalmic  goiter  at  the  time  of  their  growth 
appear  to  have  longer  bones  than  normally. 

Action  on  the  Nervous  System. — In  animals  which  have  died  following 
intensive  hyperthyroidization  no  well-defined  lesions  of  the  nervous 
system  are  found,  whereas  the  cerebrospinal  lesions  seen  in  thyroid- 
ectomized  animals  have  been  various  and  multiple.  Albertoni  and 
Tizzoni  found  peripheric  neuritis;  Weiss  and  Rogowitsch  found  anemia, 
edema  of  the  nervous  elements,  and  a  parenchymatous  encephalitis; 
Schultze  and  Schwartz  saw  a  leukocyte  infiltration  in  the  membranes 
surrounding  the  upper  portion  of  the  medulla.  Herzen  and  Lowenthal 
saw  a  vacuolar  degeneration  and  atrophy  of  the  pyramidal  cells  and 
corticalitis  of  the  region  of  the  sigmoid  gyrus,  which  is  the  motory  center 
of  the  lower  limbs.  Capobianco  saw  vacuolar  degeneration  in  both 
hemispheres  of  the  cerebellum,  in  the  bulb  and  in  the  gray  matter  of 
the  medulla.  Pisenti  and  Luppo  found  bulbar  hemorrhages.  Walter 
saw  that  thyroidectomy  interferes  with  the  regeneration  of  the  per- 
ipheric nerve  after  traumatism,  but  that  as  soon  as  thyroid  opotherapy 
is  started  the  regeneration  of  the  nerves  takes  place.  Walter  described 
marked  pathological  disturbances  in  the  hypophysis  after  complete 
thyroidectomy. 

Langhans  has  found  a  marked  degeneration  of  the  muscles  in  cretins. 
This  degeneration  is  found  in  Basedow's  disease  and  may  explain  the 
muscular  weakness  and  tremor  found  in  this  condition. 

Modification  of  the  Urine. — In  myxedema  the  quantity  of  urine  is 
diminished  and  its  toxic  properties  are  increased.  According  to  Pagenoff 
this  toxicity  of  the  urine  is  due  to  the  same  leukomain  which  he  found 
in  the  blood  of  thyroidectomized  animals.     In  the  urine  and  thyroid  of 


MODIFICATION  OF  THE   URIXE  41 

Basedow's  patients,  toxic  products  have  been  isolated  by  Bovnet  and 
Silbert.  The  excretion  of  phosphorus  in  urine  diminishes  markedly  after 
total  thyroidectomy.  Sugar,  which  is  very  often  found  in  exophthalmic 
goiter,  seldom  appears  in  myxedematous  conditions.  It  is  well  known 
that  in  Basedow's  patients  alimentary  glycosuria  is  easily  produced, 
whereas  patients  with  hypothyroidism  can  stand  large  doses  of  sugar 
without  showing  glycosuria. 

Albumin  is  sometimes  found  in  great  quantities  after  complete 
thyroidectomy,  but  Corronedi  claims  that  albuminuria  is  caused  bv  the 
fact  that  with  the  thyroid  the  parathyroids  have  been  simultaneously 
removed,  and  that  albuminuria  is  a  symptom  of  parathyroid  insufficiency 
and  does  not  occur  when  the  parathyroids  have  been  left  uninjured. 

Robert  Hutchinson  in  a  revision  of  the  literature  upon  the  effects  of 
thyroid  extractives  on  metabolism  says:  "It  may  be  said  that  the  effect 
of  the  administration  of  thyroid  is  to  increase  the  oxidation  of  the  body; 
it  makes  the  tissues,  as  it  were,  more  inflammable,  so  that  they  burn 
away  more  rapidly.  The  products  of  the  disintegration  of  the  nitrog- 
enous tissues  appear  in  the  urine  almost  entirely  in  the  form  of  urea, 
uric  acid,  and  the  xanthin  bases,  while  the  products  of  the  fat  destruction 
are  eliminated  as  CO2  by  the  lungs  and  water  by  the  kidneys." 

Lnderhill  and  Faiki  found  that  after  complete  thyroidectomy  the 
ammonia  output  in  the  urine  was  increased  even  beyond  what  is  observed 
in  starving  animals.  Nitrogen  in  the  urine  is  eliminated  under  the  form 
of  kreatin,  punn  bodies,  allantoin.  They  found  that  thyroidectomized 
dogs  are  incapable  of  utilizing  subcutaneously  introduced  dextrose  in 
anywhere  near  the  same  degree  as  normal  animals;  that  thyroid  tissue 
fed  to  normal  animals  causes  a  slight  increase  in  the  urinary  nitrogen 
excretion,  and  that  this  influence  soon  disappears  when  the  thyroid 
feeding  is  stopped.  Small  doses  of  thyroid  appear  to  have  as  pronounced 
an  influence  on  nitrogen  elimination  as  large  ones. 

How  much  of  the  thyroid  is  it  necessary  to  leave  in  order  to  prevent 
symptoms  of  thyroid  insufficiency?  It  has  been  demonstrated  experi- 
mentally by  Colzi,  von  Eiselsberg,  Fuhr,  etc.,  that  one-third  or  one- 
fourth  of  the  entire  gland  is  sufficient  to  prevent  myxedematous  degen- 
eration' Pincles  found  that  one-eighth  of  the  gland  was  sufficient  to 
prevent  thyroid  insufficiency  in  the  macacus.  The  remaining  portion  oi 
the  gland  left  in  situ  undergoes  a  compensatory  hypertrophy  winch  has 
been  well  described  by  Horslev  and  Halstead:  cells  begin  to  proliferate, 
become  larger  in  size,  and  undergo  a  process  of  division  forming  new 
alveoli   \uth  colloid  secretion. 


CHAPTER   III. 
BIOLOGICAL  CHEMISTRY. 

In  the  thyroid  Ordtmann  found  81.24  per  cent,  of  water,  17.66  per 
cent,  of  organic  matter,  and  0.1  per  cent,  of  inorganic  matter,  of  which 
iodin  occupies  the  most  prominent  place. 

After  iodin  had  been  discovered  by  Courtois  in  181 2,  Straub,  of 
Berne,  suggested  that  it  was  the  active  principle  of  the  "toasted 
sponges"  and  "aethiops  vegetalis,"  both  of  which  had  been  used  for 
centuries  in  goiter  therapy.  Ever  since  its  discovery  iodin  has  been 
universally  employed  in  thyroid  pathology.  In  1895,  very  much 
impressed  by  the  similarity  of  the  effects  of  iodin  and  thyroid,  Kocher 
suggested  that  it  would  be  advisable  to  examine  thyroids  for  that  ele- 
ment. These  researches,  which  were  entrusted  to  an  incompetent 
research  worker,  remained,  however,  negative.  More  fortunate  than 
Kocher,  Baumann  in  the  same  year  discovered  in  the  thyroid  an  ele- 
ment which  he  called  iodothyrin  (thyroiodin  of  Roos).  This  he  consid- 
ered as  the  active  principle  of  the  gland.  Brown  states  this  amorphous 
substance  resists  the  digestive  ferments  and  is  insoluble  in  a  10  per 
cent,  solution  of  HC1.  Its  iodin  content  varies  from  10  to  14  per  cent. 
This  nitrogenous  compound  gives  the  xanthoproteic  reaction.  Later 
researches  established  the  fact  that  this  substance  does  not  exist  as 
such  in  thyroid,  and  that  it  is  not  the  result  of  an  active  principle  in  the 
gland,  but  is  produced  artificially  by  the  brutal  action  of  sulphuric  acid 
on  the  thyroid  and  is  the  result  of  decomposition  of  iodized  substances 
contained  in  the  gland. 

Notkine  extracted  from  the  thyroid  an  albuminous  substance  which 
he  called  thyreoproteid.  Given  in  subcutaneous  injections  to  thyroid- 
ectomized  animals  it  produces  convulsions,  dyspnea,  and  death,  whereas 
given  to  normal  animals  it  causes  symptoms  resembling  those  of  cachexia 
strumipriva.  This  substance  is  not  normally  found  in  the  thyroid,  but 
is  a  toxic  product  of  metabolism,  and  is  neutralized  in  the  gland  itself. 

Hutchinson,  in  1 897,  discovered  in  the  colloid  two  different  substances : 
a  proteic  one,  scarcely  active  and  containing  very  little  iodin,  and  a  non- 
proteic  one,  with  energic  properties,  and  rich  in  iodin  and  phosphorus. 

Oswald  isolated  from  the  thyroid  two  different  substances:  the 
thyreoglobulin  and  the  nucleoproteid.  The  first  one  may  contain  iodin 
or  may  not.  If  it  contains  iodin,  it  is  called  iodothyreoglobulin.  The 
nucleoproteid  is  free  of  iodin  but  contains  great  quantities  of  phos- 
phorus.    Both  substances  enter  for  the  most  part  into  the  composition 


BIOLOGICAL  CHEMISTRY  43 

of  colloid.  Normally,  the  human  thyroid  contains  from  i  to  9  grams  of 
thyreoglobulin  and  its  amount  increases  in  direct  proportion  to  the 
quantity  of  colloid. 

When  injected  intravenously  the  nucleoproteid  was  found  bv  Oswald 
and  von  Cvon  physiologically  inactive,  whereas  the  iodothvreoglobulin 
possesses  energetic  properties.  Its  iodin  content  varies  with  the  species 
of  animal,  1.16  per  cent,  in  the  hog,  1.86  per  cent,  in  cattle,  and  0.^4 
per  cent,  in  the  human  being.  When  thyreoglobulin  is  free  of  iodin,  as 
in  young  animals,  it  may  be  transformed  into  iodothvreoglobulin  bv 
adding  an  iodide  compound  to  the  food.  This  synthesis  is  possible  in 
the  organism  only,  as  Oswald  was  unable  to  iodize  the  thvreoglobulin 
in  vitro.  In  newborn  babes  whose  mothers  had  been  fed  with  iodin 
Nagel  and  Roos  always  found  iodin  in  their  glands,  while  thev  did  not 
find  any  in  the  thyroids  of  babes  whose  mothers  had  not  been  fed 
with  iodin  during  their  pregnancy.  Marine  and  Lenhart  have  recorded 
similar  results  for  animals.  The  quantity  of  iodin  contained  in  a  gland 
is  dependent  upon  the  quantity  of  colloid  and  upon  the  quantitv  of 
thvreoglobulin  contained  in  the  colloid. 

The  quantity  of  iodothvreoglobulin  which  can  be  extracted  from  the 
thyroid  amounts  to  a  few  grams  and  contains  about  0.5  per  cent,  of 
iodin.  How  much  of  this  substance  is  daily  secreted  by  the  thvroid  is 
extemely  hard  to  say,  but,  according  to  Oswald,  if  we  take  into  con- 
sideration the  amount  of  iodothvreoglobulin  which  was  sufficient  to  cure 
the  case  of  myxedema  reported  by  him  we  may  judge  that  in  the  adult 
this  amount  will  scarcely  exceed  0.05,  which  contains  about  nr  mg.  of 
iodin.  The  action  of  iodothvreoglobulin  must  not  be  compared  with 
iodin,  as  the  latter  has  entirely  different  pharmacodynamic  properties. 
Iodin  is  an  inorganic  compound  while  iodothvreoglobulin  is  an  organic 
albuminous  substance. 

The  nucleoproteid  of  Oswald  does  not  contain  iodin  but  contains 
0.16  per  cent,  of  phosphorus  and  arsenic.  Besides  these  elements  leuko- 
mains  have  been  found  by  Bourquelot  and  Lepinois  and  bromine  by 
Baldi.  Chamagne  was  able  to  extract  from  the  thyroid  very  toxic 
lipoids.  Albumoses,  leucin,  xanthin,  hypoxanthin,  NaCl,  sulphur, 
oxalate  of  calcium,  and  lactic  acid  are  parts  of  the  constituent  elements 
of  the  thyroid. 

The  dijodthyrosin  which  Oswald  discovered  lately  has  tin-  charac- 
teristic elements  of  iodized  albuminous  substances,  but  has  no  effect 
on  the  circulatory  apparatus  nor  on  the  nervous  system,  and  does  not 
influence  goiter  in  anv  wav,  therefore  it  cannot  be  considered  as  the 
active  principle  of  the  thyroid. 

Kendall  isolated  a  crystalline  iodin  '60  per  cent.'  compound  from 
the  thyroid  in  1914.  It  is  locked  in  the  protein  molecule  and  can  !>< 
obtained  only  under  the  influence  of  carbon  dioxid.      The  administ  ration 


44  BIOLOGICAL  CHEMISTRY 

of  this  substance  gives  all  the  effects  of  thyroid  administration.  If 
amino  acids  are  injected  simultaneously  the  pulse-rate  is  enormously 
affected;  otherwise  not.  In  general  it  affects  the  growth,  mentality, 
skin,  hemoglobin,  and  metabolism. 

lodin  in  the  Thyroid  Gland. — Iodm  is  found  not  only  in  the  thyroid 
gland,  but  can  also  be  detected  in  a  great  many  other  organs,  as  the 
muscles,  suprarenal  bodies,  hypophysis,  liver,  kidneys,  central  nervous 
system,  thymus,  spleen,  and  lymph  nodes.  We  must  admit,  however, 
that  it  is  present  in  the  thyroid  in  larger  quantities  than  in  any  other  organ 
of  the  body  except  in  the  parathyroids.  There,  according  to  Gley 
and  Lafayette,  the  quantity  of  iodin  is  even  larger  than  in  the  thyroid. 

Iodin  varies  with  the  conditions  of  life  of  animals  as  well  as  of 
patients;  it  varies,  too,  with  localities.  In  Fribourg,  Switzerland,  for 
instance,  where  goiter  is  frequent,  Baumann  found  only  traces  of  iodin 
in  7  out  of  26  glands.  Their  average  content  was  about  2  mgs.,  whereas 
10  out  of  27  glands  from  Hamburg  contained  more  than  4  mgs.  In 
Berlin  the  quantity  was  found  to  vary  from  5.3  to  8.1  mgs.  This  differ- 
ence was  more  striking  in  children.  Out  of  17  children  of  Fribourg 
from  one  day  to  seven  years  old  only  traces  were  found.  Five  times  the 
thyroid  contained  a  quantity  of  iodin  varying  from  0.7  to  0.3  mg., 
whereas  in  5  thyroids  of  children  from  Hamburg,  iodin  was  constantly 
present  in  proportion  of  0.1  to  0.45  mg. 

Iodin  content  in  the  thyroid  increases  if  the  food  contains  iodin. 
The  aliments  which  contain  most  iodin  are  asparagus,  carrots,  beans, 
mushrooms,  and  fish.  Iodin  medications  increase,  too,  the  iodin  con- 
tent of  the  thyroid.  After  the  skin  of  a  dog  had  been  rubbed  with 
iodoform,  Baumann  found  that  the  thyroid  gland  of  this  dog  contained 
0.3  mg.  Smith  and  Broders  found  that  external  applications  of  tincture 
of  iodin  increased  to  a  considerable  extent  the  iodin  content  of  the 
gland,  and  that  iodide  of  potash  given  internally  or  hypodermically 
increased  the  iodin  content  of  the  gland  very  materially.  After  ingestion 
of  bromides,  brome  is  stored  in  the  thyroid  in  the  same  way  as  iodin. 
The  amount  of  iodin  in  the  thyroid  increases  gradually  up  to  middle 
age  and  then  decreases  with  old  age.  Atherton  Seidell  and  Frederick 
Fenger  found  (loc.  cit.)  "That  a  marked  seasonal  variation  existed  in 
the  percentage  of  iodin  present  in  the  healthy,  normal-sized  glands  of 
the  sheep,  ox,  and  hog.  There  is  in  general  about  three  times  as  much 
iodin  present  in  the  months  between  June  and  November  as  in  the 
months  between  December  and  May.  The  seasonal  variation  in  the 
size  of  the  glands  was  observed  in  the  case  of  the  sheep  and  ox,  but 
not  in  that  of  the  hog.  The  glands  were  found  to  be  larger  in  the  months 
during  which  the  lower  iodin  content  was  noticed." 

Iodin  is  not  invariably  present  in  the  thyroid.  Miwa,  Stoeltzner 
and  Baumann  and   other  investigators   have  pointed   out  the  frequent 


IODIX  IX  THE  THYROID  GLAXD  45 

absence  of  iodin  in  the  thyroids  of  children,  of  dogs  fed  on  meat,  and  in 
those  of  cattle  and  other  animals.  They  believe  that  iodin  found  in  the 
thvroid  has  no  more  significance  than  the  traces  of  copper  found  in  the 
liver,  and  that  its  presence  or  absence  and  its  quantity  are  dependent 
upon  the  food  of  the  animal.  In  herbivorous  animals  iodin  is  found  in 
greater  quantities  than  in  carnivorous,  because  vegetables  contain 
iodin  in  greater  or  less  quantity;  whereas  no  iodin  or  very  little  is  found 
in  carnivorous,  since  pure  meat  diet  contains  no  iodin  or  very  little. 
Animals  fed  near  the  sea  show  a  double  amount  of  iodin  than  do  those 
pastured  in  inland  regions,  because  vegetable  food  along  the  coast  is 
richer  in  iodin  than  that  found  in  the  interior.  Topfer,  of  Vienna, 
found  no  iodin  in  the  thyroids  of  cattle;  Roos,  none  in  the  thyroids  of 
dogs,  none  in  that  of  the  wild-cat,  none  in  that  of  the  pole-cat,  and  found 
it  in  but  two  out  of  six  martens.  It  was  absent  from  the  thyroids  of  4 
domestic  cats  and  traces  only  were  found  in  those  of  5  others.  None 
was  found  in  4  out  of  11  dogs  nor  in  2  out  of  4  horses.  Weiss,  after 
examining  the  thyroids  of  7  children  under  four  and  a  half  years  of  age, 
found  that  the  iodin  content  varied  from  traces  to  0.37  per  cent.  Wells, 
in  analyzing  the  thyroids  of  6  children  from  Chicago,  found  that  the 
glands  of  3  had  from  traces  to  0.092  per  cent.;  the  other  3  had  0.11  per 
cent.  Yon  Rositzky  noticed  in  children  under  ten  years  of  age  that  iodin 
in  the  thyroids  varied  from  0.012  to  0.041  per  cent.  Oswald,  in  5  chil- 
dren from  Basel  under  seven  years  of  age,  found  from  traces  to  0.16 
per  cent.  Charrin  and  Bourcet  found  in  the  thyroids  of  infants  under 
three  months  from  0.0004  to  0.0054  per  cent.  Mendel  found  no  iodin 
in  the  thyroids  of  4  infants  and  found  0.07  mg.  in  others.  John  found 
in  27  children  from  Sweden  under  four  years  of  age  no  distinct  traces 
of  iodin  and  in  7  cases  from  traces  to  0.086  per  cent.  Nigel  and  Roos 
found  no  traces  of  iodin  in  the  thyroids  of  4  newborn  puppies.  ^  et 
animals  as  well  as  human  beings  in  which  iodin  was  totally  absent  or 
found  in  traces  only  were  in  just  as  good  condition  as  the  ones  whose 
thyroids  contained  a  higher  percentage  of  iodin.  Never  have  the  chil- 
dren or  animals  in  which  iodin  proved  to  be  absent  shown  any  indica- 
tion of  thyroid  insufficiency.  The  hen's  egg  does  not  contain  iodin 
when  the  young  chick  begins  its  life,  yet  its  development  seems  to  go 
on  normally.  The  same  is  true  for  the  human  newborn.  It  is  not  pos- 
sible to  detect  any  pathological  difference  between  animals  winch  have 
a  high  percentage  of  iodin  in  their  thyroids  and  those  which  contain 
none.  I  he  thyroid  free  from  iodin  seems  to  meet  the  needs  of  the  body 
just  as  well  as  the  thyroid  which  contains  iodin.  Thyroidectomy  is 
followed  by  as  severe  symptoms  in  the  latter  case  as  in  the  former. 
1  herefore  many  authors  conclude  that  iodin  is  not  necessary  for  the 
physiological  activity'  of  the  gland,  that  it  is  not  the  active  principle  of 
the  thyroid,  and  that  it  is  onlv  an  accidental  constituent  of  its  secretion. 


46  BIOLOGICAL  CHEMISTRY 

Hutchinson  corroborated  these  conclusions.  After  having  prepared  an 
artificially  iodized  nucleo-albumin  from  the  thymus  of  the  calf,  sam- 
ples of  which  contained  from  4  to  7  per  cent,  of  iodin,  he  found  it  inac- 
tive in  the  treatment  of  myxedema  and  without  effect  upon  the  pulse, 
temperature,  or  weight  of  the  subjects  to  whom  it  was  administered. 
Blum  and  Hellin  also  found  that  iodized  albumin  was  physiologically 
inactive.  They  consequently  concluded,  too,  that  iodin  does  not  play 
any  important  part  in  the  physiological  function  of  the  thyroid. 
Because  an  organ  contains  a  physiologically  active  substance  it  does 
not  follow  that  its  physiological  activity  is  due  to  that  substance;  for 
instance,  we  know  that  the  thyroid  contains  arsenic  in  larger  quantities 
than  many  other  organs,  yet  nobody  will  claim  that  arsenic  is  the  active 
principle  of  the  thyroid,  although  arsenical  preparations  are  all  very  active. 

In  1899  Roos  was  the  first  to  take  exception  to  such  views  and 
reported  the  results  of  experiments  tending  to  show  there  is  a  direct 
relation  between  the  iodin  content  and  the  influence  of  the  thyroid 
upon  metabolism.  He  gave  to  a  dog  5  mgs.  of  children's  desiccated 
thyroid  containing  0.025  Per  cent,  of  iodin.  No  effects  upon  the  excre- 
tion of  nitrogen  nor  upon  the  body  weight  were  noticed.  Another  dose 
of  5  mgs.  of  children's  thyroid  containing  0.18  per  cent,  of  iodin  was 
found  to  cause  an  excretion  of  nitrogen  of  about  10  per  cent.;  and  as 
the  same  proportion  of  iodin  contained  in  the  thyroid  increased,  the  effect 
upon  the  metabolism  became  proportionately  more  marked.  Von  Cyon 
and  Oswald  found  that  thyreoglobulin  free  of  iodin  obtained  from 
goiterous  calves  had  no  effect  upon  the  circulation,  but  became  active 
in  direct  proportion  to  its  iodin  content.  Marine  and  Williams  in  two 
experiments  fed  desiccated  sheep  thyroid  containing  different  per- 
centages of  iodin  to  dogs  and  found  that  the  loss  of  weight  of  the  animal 
was  in  proportion  to  the  quantity  of  iodin  in  the  thyroid  fed. 

Des  Ligneris  demonstrated  that  iodin  taken  by  mouth  or  given 
externally  to  young  dogs  causes  in  parenchymatous  glands  an  increase 
of  colloid,  the  folliculi  became  distended,  the  epithelium  flattened,  and 
the  blood  supply  diminished.  The  same  experiments  made  upon  old 
dogs  had  very  little  or  no  effect  at  all  upon  the  amount  of  colloid;  in 
grown  dogs  with  colloid  glands  iodin  did  not  increase  the  amount  of 
colloid.  Everybody  knows  Halstead's  classical  experiment:  If  a  portion 
of  thyroid  is  removed,  the  remaining  portion  of  the  gland  reacts  by 
secondary  hypertrophy  characterized  by  diminution  or  absence  of  the 
colloid  secretion,  hyperplasia  of  the  epithelium,  and  increased  vascu- 
larization. But  if,  soon  after  partial  thyroidectomy  has  been  performed, 
iodin  is  administered  to  these  animals  no  secondary  hypertrophy  takes 
place;  if  iodin  is  given  previously  and  then  only  partial  thyroidectomy 
is  performed,  very  little  or  no  hypertrophy  takes  place. 


IODIX  IN   THE  THYROID  GLAXD  47 

Marine  and  Lenhart  not  only  confirmed  these  results  but  went  a 
step  farther  and  claimed  there  is  a  constant  relation  between  iodin  con- 
tent and  the  structure  of  the  gland.  The}'  demonstrated  that  although 
it  is  true  that  in  Halstead's  experiments  iodin  will  prevent  secondary 
hypertrophy,  it  will  not  have  this  effect  if  a  maximum  of  thvroid  is 
removed;  compensatory  hypertrophy  will  then  take  place  just  the  same. 
In  order  to  produce  these  changes  the  amount  of  iodin  does  not  need 
to  be  very  large;  the  smallest  doses  are  very  effective.  The  same 
authors  believe  (loc.  cit.)  "that  the  organism  retains  iodin  in  the  same 
manner  in  which  it  retains  iron  and  calcium.  The  difference  between 
the  maximum  and  minimum  of  iodin  found  to  be  compatible  with  the 
maintenance  of  the  normal  histological  structure  represents  the  excess 
of  intake  or  consumption.  If  iodin  falls  below  a  quite  constant  level, 
the  gland  undergoes  characteristic  and  constant  histological  changes, 
while  if  iodin  is  given  these  changes,  either  do  not  occur,  or  if  they  have 
started,  they  are  arrested.  It  is  of  little  or  no  consequence  whether 
hyperplasia  occurs  in  man  or  animal,  or  whether  it  is  associated  clini- 
cally with  myxedema  or  exophthalmic  goiter.  In  the  presence  of  suffi- 
cient doses  of  iodin  all  true  hyperplasia  is  prevented." 

I  do  not  know  how  far  these  conclusions  are  correct,  but  they  cer- 
tainly do  not  correspond  to  what  we  see  in  our  daily  practice.  From 
the  above  statements  we  have  the  right  to  infer  that  glandular  hyper- 
plasia found  in  Graves'  disease  is  due  to  a  "more  or  less  marked  lack 
of  iodin,"  that  the  severity  of  the  disease  is  in  direct  proportion  to  the 
diminution  or  absence  of  iodin  in  the  gland,  and  consequently  that 
iodin  treatment  is  the  only  logical  treatment  of  the  condition.  Nothing 
has  been  less  demonstrated  than  that  "lack  of  iodin"  is  the  cause  of 
Basedow's  disease,  and  that  its  severity  is  proportional  to  its  presence 
or  absence;  on  the  other  hand,  nothing  has  been  better  demonstrated 
than  that  iodin  is  not  the  specific  treatment  of  exophthalmic  goiter. 
More  so,  in  the  great  majority  of  cases  it  is  harmful.  Yet  it  cannot  be 
denied  that  Iodin  will  prevent  secondary  glandular  hyperplasia,  as  in 
Halstead's  experiment.  Why  such  inconsistency  ?  Very  likely  simply 
because  glandular  hyperplasia  in  Graves'  disease  and  glandular  hyper- 
plasia found  as  a  compensatory  process  after  partial  extirpation  <>t  the 
gland  an-  due  to  two  absolutely  different  conditions  corresponding  to 
two  absolutely  different  processes.  Similar  does  not  mean  identical, 
and  because  glandular  hyperplasia  in  both  conditions  has  a  histological 
resemblance,  nothing  proves  that  their  chemicopathological  functions 
arc  tin-  same. 

Although  variable  in  its  limits,  the  highest  iodin  content  per  gram  is 
Found  in  normal  glands.  Whether  these  variations  are  due  to  varia- 
tions  in    the   intake  or   to   the   consumption    within    the   organism   or   to 


48  BIOLOGICAL  CHEMISTRY 

both  is  not  known.  More  probably  they  depend  upon  the  intensity  of 
the  chemicobiological  metabolism  whose  intensity  varies  with  each  given 
individual. 

In  parenchymatous  and  exophthalmic  goiter  the  amount  of  iodin 
varies  inversely  with  the  degree  of  glandular  hyperplasia;  consequently, 
the  lowest  amount  of  iodin  will  be  found  with  the  highest  degree  of 
hyperplasia.  Yet  Oswald,  Caro,  Smith  and  Broders,  myself  and  others 
have  observed  cases  of  Graves'  disease  in  which  the  iodin  content 
was  remarkably  high.  As  in  marked  hyperplastic  conditions  colloid  is 
generally  absent  or  very  much  diminished,  we  can  say  that  iodin  varies 
in  direct  proportion  to  the  amount  of  stainable  colloid.  Aesbacher 
strengthened  these  views  by  finding  a  diminished  iodin  content  in  alco- 
holic intoxication  and  in  acute  inflammatory  diseases  of  the  thyroid. 
This  was  to  be  expected,  as  we  shall  see  in  the  chapter  on  Bacterial  and 
Toxic  Thyroiditis,  that  in  such  conditions  there  existed  at  the  same 
time  a  glandular  hyperplasia  and  a  diminution  of  colloid.  Claude  and 
Blanchetiere,  however,  refuse  to  see  any  such  parallelism  between  col- 
loid and  iodin,  as  they  have  found  high  iodin  content  in  glands  where 
no  colloid  was  present.  It  is  very  well  agreed  that  colloid  glands  in 
general  contain  less  iodin  than  normal  glands,  although  to  this  there 
are  many  exceptions,  as  shown  by  Oswald.  In  fetal  adenoma  Marine 
and  Williams  found  iodin  and  there,  too,  the  iodin  content  was  in  direct 
proportion  to  the  glandular  hyperplasia.  The  total  amount  of  iodin 
that  a  gland  may  contain  depends  upon  its  size,  the  diet,  locality,  medi- 
cation, etc.  As  regards  the  iodin  content  in  human  thyroids  of  cretins,  no 
specific  observations  are  recorded,  but  as  these  glands  are  atrophied,  we  can 
assume  that  the  iodin  content  must  be  low.  In  old  age  there  is  a  slight 
decrease  of  iodin  seemingly  proportionate  to  the  degree  of  senile  atrophy. 

Be  that  as  it  may,  the  fact  becomes  more  and  more  evident  that 
iodin  must  not  be  regarded  as  purely  accidental,  but  that  it  plays  some 
important  function  in  metabolism.  The  merits  of  having  come  nearer 
the  solution  of  this  problem  certainly  belong  to  Reid  Hunt  and  Atherton 
Seidell.  In  extremely  elegant  and  conclusive  experiments  they  demon- 
strated that  if  small  amounts  of  thyroid  are  fed  to  mice  for  a  few  days, 
these  animals  acquire  a  markedly  increased  resistance  to  acetonetrile. 
Thus,  a  mouse  which  had  been  fed  with  thyroid  for  nine  or  ten  days 
recovered  from  seventeen  times  the  relative  amount  of  acetonetrile  fatal 
to  the  controls;  hence  the  conclusion  that  thyroid  enables  the  mouse 
to  "neutralize"  or  resist  in  some  way  doses  of  acetonetrile  which  in 
ordinary  conditions  are  fatal.  From  another  series  of  experiments  it 
was  found  that  if  one  part  of  iodothyrin  was  fed  to  a  mouse  for  ten  days, 
it  enabled  the  mouse  to  resist  more  than  240  times  an  equal  amount  of 
acetonetrile. 


IODIX  IX   THE  THYROID  GLAXD  49 

Up  to  that  time  iodin-free  thyroids  were  regarded  as  being  deprived 
of  their  physiological  activity.  \\  ith  their  delicate  tests  the  same 
authors  were  able  to  demonstrate  that  this  is  not  the  case.  They  found 
that  iodin-free  thyroids  have  a  low  degree  of  physiological  activity, 
that  their  activity  is  lower  than  the  thyroids  containing  iodin,  and  that 
their  physiological  properties  increase  in  direct  proportion  to  the  amount 
of  iodin.  Consequently,  it  may  be  concluded  that  the  activity  of  iodin- 
free  thyroids  is  nevertheless  largely  due  to  the  iodin  present  in  too  small 
quantities  to  be  detected,  or  that  the  iodin-free  thyreoglobulin  has  of  itself 
some  physiological  properties.  The  latter  possibility  would  explain  why  in 
Hunt's  and  Seidell's  experiments  certain  iodin-free  thyroids  were  more 
active  than  thyroids  containing  small  amounts  of  iodin.  It  may  be 
supposed  that  iodin-free  or  iodin-poor  thyroids  can  meet  the  ordinary 
demands  of  the  organism;  but  if  the  demands  upon  the  thyroid  are 
not  adequate  to  the  function  of  the  iodin-free  gland,  marked  symptoms 
of  hypothyroidism  will  follow,  as  shown,  for  example,  by  the  losses 
suffered  by  sheep  breeders  on  account  of  cretin  lambs  before  the  exten- 
sive use  of  lodin-containing  salt. 

Continuing  their  experiments,  Hunt  and  Seidell  found  that  the 
resistance  of  rats,  mice,  and  guinea-pigs  to  morphin  is  uniformly  low- 
ered after  thyroid  feeding.  In  the  case  of  rats  there  is  a  close  parallelism 
between  the  physiological  effect  of  the  thyroid  as  determined  by  the 
increased  susceptibility  to  morphin  and  the  percentage  of  iodin.  A 
similar  parallelism  was  found  in  general  in  experiments  on  mice.  Ani- 
mals which  had  received  thyroid  with  a  higher  percentage  of  iodin 
showed  a  better  resistance.  There  is  no  explanation  for  the  cause  of 
this  increased  susceptibility. 

If  we  sum  up  the  results  of  these  experiments  and  weigh  them,  it 
cannot  be  denied  that  a  fact  stands  forth  most  strikingly,  namely,  that 
iodin  seems  to  be  of  great  importance  in  the  thyroid's  physiological 
activity.  This  is  so  true  that  Oswald  considers  iodothyreoglobulin  as 
the  active  principle  of  the  secretion,  because,  according  to  him,  it 
possesses  all  the  physiological  properties  of  the  thyroid.  As  we  know, 
one  of  the  most  important  properties  of  the  gland  is  to  cure  spontaneous 
as  well  as  operative  myxedema.  Now  then,  Oswald  treated  a  young 
myxedematous  boy,  eighteen  years  old,  measuring  131  cms.  in  length. 
He  gave  the  boy  a  daily  dose  of  0.1  gm.  of  iodothyreoglobulin  for  twenty- 
one  months.  During  that  period  of  treatment  the  patient  grew  21  cms., 
lost  his  cretinoid  appearance,  and  improved  in  every  respect,  mentally 
as  well  as  physically.  Pick  and  Pineles  have  come  to  the  same  conclu- 
sions experimentally.  Another  property  of  the  thyroid  is  to  increase 
oxidation  of  fat  and  albumin.  This  property  is  found,  too,  in  iodothyreo- 
globulin. Thyroid  extract  increases  the  susceptibility  of  the  vagus 
4 


50  BIOLOGICAL  CHEMISTRY 

fibers  to  the  faradic  current;  iodothyreoglobulin  does  the  same.  Accord- 
ing to  Oswald  no  other  substance  in  the  thyroid  has  a  single  one  of  the 
same  properties  as  the  iodothyreoglobulin,  and  these  properties  are  due 
to  the  iodin  combined  with  a  globulino-albuminoid  substance. 

Is  it  really  so  ?  Is  it  really  to  iodin  that  thyreoglobulin  owes  its 
physiological  properties  and  is  iodothyreoglobulin  the  true  active  prin- 
ciple of  the  gland  ?  The  question  is  not  settled:  Baumann  and  Hutchin- 
son, Oswald,  Gauthier  and  others  say,  "Yes,"  whereas  Fraenkel, 
Dreschel,  Gottlieb,  Chassavant,  Hunt,  Seidell,  etc.,  claim  that  the 
iodized  proteids  are  not  the  only  ones  possessing  physiological  activity. 
Most  probably  each  camp  holds  a  part  of  the  truth;  neither  one  of  the 
compounds  can  be  considered  as  representing  the  whole  active  prin- 
ciple of  the  thyroid  gland;  there  must  be  other  compounds  endowed,  too, 
with  some  physiological  properties.  This  is  suggested  by  the  fact  that 
every  kind  of  thyroid  preparation,  and  they  are  numerous,  has  some 
of  the  physiological  properties  of  the  thyroid,  and  that  the  thyroid 
in  toto  given  as  medication  has  succeeded  where  iodized  preparations 
have  failed. 

If  iodin  plays  an  important  part  in  the  clinical  function  of  the  thy- 
roid secretion,  we  must  not  forget  that  there  are  in  the  thyroid  other 
chemical  compounds  to  w7hich  not  enough  consideration  has  been  given. 
Arsenic,  for  example,  as  previously  said,  exists  constantly  in  the  thyroid, 
and  is  present  in  that  gland  in  quantities  larger  than  in  any  other  organ 
of  the  body.  Certainly  its  presence  is  not  an  accidental  one;  it  must 
play  a  part  in  the  physiological  activity  of  the  gland.  In  nature  arsenic 
and  iodin  do  not  exclude  each  other;  on  the  contrary,  they  are  most 
frequently  found  associated;  sulphurous  and  iodized  waters  contain 
arsenic;  algae,  for  instance,  contain  iodin  and  arsenic  always  mixed 
together.  Furthermore,  iodin  combined  with  arsenic  is  always  an 
excellent  thyroid  medication.  According  to  A.  Gauthier  arsenic  is 
found  in  the  thymus,  skin,  brain,  and  hypophysis,  but  nowhere  else. 
Is  this  only  a  coincidence,  or  has  it  a  greater  significance  than  it  seems 
to  have  at  first?  The  answer  is  not  yet  at  hand,  but  it  will  be  inter- 
esting to  note  that  the  thymus,  brain,  skin,  and  hypophysis  are  pre- 
cisely the  organs  electively  involved  in  thyroid  disturbances. 

Phosphorus  is  constantly  present  in  the  thyroid.  According  to 
Bayer  5  gms.  of  fresh  thyroid  contains  0.00102  gm.  of  P2O5  (pentoxide 
of  phosphorus).  Kocher  regards  phosphorus  as  playing  an  important 
part  in  thyroid  physiology.  There  seems  to  exist  an  antagonistic  action 
between  iodin  and  phosphorus. 

Brisson,  who  has  investigated  the  sulphur  content  of  several  endo- 
crine glands,  found  0.23  gm.  of  baryte  sulphide  per  2  gms.  of  thyroid. 
The  organs  which  contain  the  greatest  quantity  of  sulphur  are  the 
suprarenal  bodies,  testicles,  and  keratine. 


CONCLUSIONS  CONCERNING  THE  THYROID  FUNCTION         51 

In  the  thyroid  Iscovesco  found  lipoids,  which  possess  a  very  ener- 
getic physiological  action.  According  to  him  there  is  in  the  organs  of 
vertebrates  a  specific  and  unique  lipoid  which,  injected  into  the  organ- 
ism of  an  animal,  has  the  property  of  localizing  its  action  on  the  organ 
from  which  it  originates  and  on  this  one  only.  These  lipoids  are  called 
homostimulants  because  the}'  exert  their  action  by  an  elective  influence 
on  the  medullar  centers  controlling  the  organ  from  which  they  derive. 
One  of  these  lipoids,  called  by  Iscovesco  thyrol  A,  injected  hypodermi- 
callv  produces  exophthalmos,  tachycardia,  and  swelling  of  the  thyroid; 
another  lipoid  when  given  in  doses  of  2  cgms.  per  kilogram  produces 
cachexia. 

The  activity  of  the  gland  was  thought  to  depend  upon  its  ferments, 
and  lately  Youchtchenko  showed  that  the  thyroid  secretion  contains  a 
great  quantity  of  catalase  and  peroxydase.  These  ferments  preside  over 
the  oxygen  exchanges  in  the  organism.  In  carnivorous  animals  he  found 
in  the  thyroid  a  certain  amount  of  lipase,  a  ferment  which  intervenes  in 
the  metabolism  of  fat.  This  would  explain  certain  conditions  found  in 
hypo-  and  hyperthyroidism.  In  hypothyroidism  the  peroxydasic  and 
lipasic  ferments,  being  diminished  on  account  of  the  reduced  function  of 
the  thyroid,  oxydative  processes  will  be  diminished,  hence  the  sensation 
of  cold,  adipositas,  etc.;  on  the  other  hand,  in  exophthalmic  goiter  the 
cellular  activity  being  increased,  the  ferments  are  in  greater  quantity; 
consequently  the  metabolism  is  accelerated;  hence  the  sensation  of 
heat,  elevated  bodily  temperature,  loss  of  flesh,  etc. 

In  summing  up  we  see  that  the  pharmacodynamic  function  of  the 
thyroid,  as  of  other  organs,  the  liver,  for  instance,  is  not  one  but  is  mul- 
tiple; it  seems  therefore  logical  to  ascribe  to  the  thyroid  several  func- 
tions: an  iodin  function  presiding  over  the  general  metabolism;  a  phos- 
phorus junction  presiding  over  the  thermogenesis  and  over  the  vaso- 
motor)' system  regulating  the  cardiac  rhythm;  a  sulphurus  Junction 
presiding  over  the  nutrition  of  the  skin  and  the  pileus  system;  and  an 
arsenical  function  presiding  over  the  nervous  function  and  whose  insuffi- 
ciency causes,  according  to  Hertoghe,  migraine.  Most  likely  every  one 
of  these  functions  takes  place  through  a  special  hormone. 

Conclusions  Concerning  the  Thyroid  Function  and  its  Chemistry.  The 
thyroid  is  an  organ  necessary  to  life  and  plays  an  important  part  in  metab- 
olism. It  presides  over  the  nutritional  exchanges,  over  the  osseous  growth, 
and  regulates  the  nervous  and  vascular  systems.  Its  insufficiency  causes 
hypothyroidism.  To  this  condition  belong  not  only  myxedema  and 
cretinism,  but  also  a  large  series  of  intermediate  stages  called  by 
Hertoghe  "form  frustes,"  and  characterized,  as  we  will  see  later,  by 
disturbances  in  the  sexual  apparatus,  gastro-intestirral  tract,  osseous 
system,  etc.      These  disturbances  may  be  more  or  less  marked;  mam    of 


52  BIOLOGICAL  CHEMISTRY 

them   may  be   present   at   the  same   time,   or  only  one  symptom   may 
betray  a  light  degree  of  thyroid  insufficiency. 

Thyroid  and  parathyroids  differ  not  only  embryologically  and 
anatomically,  but  are  also  functionally  two  different  organs.  Complete 
removal  of  the  thyroid  gland  produces  chronic  nutritional  disturbances, 
as  retarded  osseous  growth,  myxedematous  infiltration  of  the  skin, 
marked  reduction  in  general  metabolism,  with  profound  psychic  dis- 
turbances. On  the  other  hand,  complete  parathyroidectomy  causes 
acute  nervous  conditions,  as  convulsions,  tetany,  which  soon  terminate 
in  death.  At  the  same  time,  hyperthermy,  tachycardia,  and  dyspnea, 
as  found  in  acute  intoxications,  are  present. 

What  is  the  active  principle  of  the  gland  ?  We  may  say  that  this 
active  principle  is  not  one  but  is  multiple.  The  one  which  we  know 
best  is  iodothyreoglobulin.  It  is  regarded  by  many  as  the  real  and  only 
active  principle  of  the  thyroid.  This,  however,  has  not  been  sufficiently 
demonstrated.  No  doubt  it  plays  a  very  important  part  in  metabolism 
and  controls  to  a  great  extent  the  growth  of  the  osseous  system;  better 
than  any  other,  this  substance  embodies  the  best,  the  physiological, 
action  of  the  thyroid  itself.  But  it  is  not  the  only  one;  there  are  other 
substances  in  the  thyroid  which  are  physiologically  important;  there  is  a 
phosphorus  principle  presiding  over  the  vasomotory  system  regulating 
the  cardiac  rhythm  and  thermogenesis.  We  have  also  seen  that  there  is 
a  sulphurous  principle  presiding  particularly  over  the  nutrition  of  the 
skin  and  pileus  system.  Finally,  there  is  an  arsenical  principle  which 
has  a  certain  action  over  the  nervous  system.  Every  one  of  these  prin- 
ciples represents,  we  may  say,  a  special  hormone.  How  these  different 
hormones,  and  very  likely  others  which  we  have  not  yet  discovered, 
exert  their  action  and  where  is  not  known.  Shall  we  consider  them  as 
excitants  of  the  cellular  nutrition  facilitating  the  assimilative  process,  or 
shall  we  consider  them  as  substances  necessary  to  the  cell  itself  and  its 
functions,  just  as  traces  of  zinc  seem  to  be  an  absolutely  necessary 
aliment  for  the  aspergillus  niger?    The  answer  is  still  not  at  hand. 

Biedl  thinks  that  there  are  in  the  thyroid  two  hormones  which  he 
calls  dissimilatory  and  assimilatory.  According  to  him  the  dissimilatory 
hormones  activate  the  normal  activity  of  the  organs,  of  the  heart,  of 
metabolism,  of  the  adrenals,  of  hypophysis,  etc.  The  assimilatory  hor- 
mones, on  the  contrary,  paralyze  a  great  many  organs  and  functions,  as 
the  growth  of  bones,  the  function  of  the  pancreas,  etc. 

The  fact  that  thyroid  substances  resist  the  action  of  the  stomachal 
and  intestinal  digestive  ferments  shows  that  its  main  active  principle  is 
more  than  an  albuminous  substance.  Certainly  it  is  difficult  to  admit 
that  the  ferments  as  catalase,  peroxydase,  and  lipase  found  in  the  thy- 
roid have  no  pathological  significance  and  that  their  presence  in  that 


COXCLUSIOXS  COXCERXIXG  THE  THYROID  FUNCTION         53 

organ  is  purely  accidental.  These  ferments  preside  over  the  oxygen 
exchanges  and  intervene  in  the  metabolism  of  fat.  The  same  may  be 
asserted  for  the  lipoids;  they  certainly  must  play  some  part  in  the  very 
complicated  biological  chemistry  of  the  thyroid.  Consequently,  we  see 
that  the  thyroid  function  is  not  one  but  is  multiple,  and  is  an  extremely 
important  one. 

How  does  this  gland  exert  its  influence  over  the  metabolism  ?  A 
great  majority  of  authors  believe  that  the  gland  has  an  antitoxic  action 
and  that  it  secretes  substances  which  neutralize  poisons  resulting  from 
metabolism.  This  was  the  opinion  of  SchifFand  seems  to  be  corroborated 
by  the  fact  that  intense  bleeding  in  thyroidectomized  animals  dimin- 
ishes the  intensity  of  hypothyroidism  symptoms.  Intravenous  injection 
of  salt  solution  does  the  same  thing.  We  may  consequently  infer  that 
toxic  products  have  been  partly  eliminated  with  the  bleeding  or  dis- 
solved by  the  physiological  solution  injected. 

Notkine  believes  that  the  thyreoproteid  is  the  toxin  which  is  the  real 
cause  of  myxedema,  and  that  the  physiological  action  of  the  thyroid 
consists  in  neutralizing  the  thyreoproteid  contained  in  the  organism. 
Fraenkel  believes  that  the  neutralizing  agent  is  the  thyro-antitoxin, 
Baumann  thinks  that  it  is  the  iodothyrin,  and  Oswald  the  iodothyreo- 
globulin.  Von  Cvon  believes  that  the  principal  function  of  the  thyroid 
is  to  transform  iodin  compounds  into  a  harmless  organic  combination, 
the  iodothyrin;  Blum,  that  the  thyroid  neutralizes  in  the  gland  itself  the 
toxic  products  of  intestinal  origin,  the  enterotoxins.  According  to  him 
there  is  in  the  thyroid  an  intermediary  product  which  he  calls  thyro- 
toxalbumin,  whose  antitoxic  power  is  due  to  iodin.  As  it  is  possible  to 
obtain  from  the  thyroid  various  albuminous  bodies  with  a  varying 
iodin  content,  Blum  believes  that  bodies  poor  in  iodin  are  the  more 
poisonous,  that  the  ones  containing  the  most  iodin  are  non-poisonous 
and  non-toxic,  and  that  the  ones  saturated  with  iodin  are  harmless. 
On  the  nature  and  quantity  of  these  various  by-products  reaching  the 
circulation  depend  the  various  clinical  conditions,  as  tetany,  cachexia, 
etc.  Blum  does  not  make  a  difference  between  the  thyroid  and  the 
parathyroids;  he  considers  the  latter  glands  as  the  younger  forms  of 
the  thyroid.  According  to  him  iodin  never  leaves  the  thyroid  to  go 
into  the  organism,  which  statement  he  thought  he  proved  by  feeding 
dogs  with  an  iodin-free  diet  for  months;  yet  at  the  end  of  that  time  he 
was  still  able  to  find  iodin  in  the  thyroid.  Cachexia,  myxedema,  and 
tetany  are  the  results  of  an  antithyreotoxin,  the  thyroid  being  unable 
to  neutralize  such  products.  Dor  claims  that  iodin  is  transformed  into 
an  organic  combination  which  in  the  general  metabolism  plays  the  role 
of  a  ferment.  Kishi  believes  that  the  thyroid  neutralizes  the  toxic  prod- 
ucts of  metabolism,  especially  the  ones  of  muscular  origin,  and   that  it 


54  BIOLOGICAL  CHEMISTRY 

destroys  the  nucleoproteids,  which  are  of  cellular  origin,  and  which  are 
introduced  into  the  organism  with  the  food.  When  neutralized,  these 
toxic  substances  are  eliminated  later  on  through  the  kidneys. 

Where  does  this  antitoxic  power  take  place  ?  Does  it  take  place  in 
the  thyroid  or  outside  ?  Shall  we  consider  this  gland  as  a  great  chemical 
laboratory  where  the  most  important  and  most  delicate  reactions  take 
place?  Or  shall  we  consider  it  as  a  filter,  a  sort  of  "clearing-house" 
where  everything  is  carefully  revised  ?  As  the  thyroid  is  a  glandular 
organ  and  not  a  lymphoid  one  it  is  difficult  to  accept  the  opinion  that 
the  detoxicatory  action  takes  place  in  the  thyroid  itself.  On  the  other 
hand,  the  fact  that  thyroid  given  by  mouth,  rectum,  or  any  other  way 
is  physiologically  active  shows  that  most  probably  the  thyroid  secre- 
tion exerts  its  action  outside  of  the  gland.  This  antitoxic  theory, 
however,  is  not  entirely  satisfactory. 

Lindemann,  studying  the  effects  of  caffeine  when  injected  into  the 
carotid  artery  of  thyroidectomized  animals,  found  that  the  dose  neces- 
sary to  kill  a  dog  so  treated  was  ten  times  larger  than  the  one  neces- 
sary to  kill  the  control.  We  have  seen  that  R.  Hunt  and  A.  Seidell  found 
that  mice  which  had  been  fed  with  thyroid  for  eight  or  nine  days  before 
were  able  to  stand  a  dose  of  acetonetrile  ten  to  twenty  times  larger  than 
the  one  necessary  to  kill  the  control. 

How  to  explain  these  results  ?  Of  course  the  partisans  of  the 
"detoxicatory  theory"  will  claim  that  acetonetrile  was  neutralized  and 
consequently  rendered  harmless,  but  Hunt  and  Seidell  do  not  share  the 
same  view  and  believe  that  the  function  of  the  thyroid  in  such  cases 
prevented  the  formation  of  the  poison  from  mtnle  because  they  found 
that  the  thyroid  had  no  effect  upon  the  toxicity  of  hydrocyanic  acid 
itself,  which  is  the  poison  resulting  from  decomposition  of  acetonetrile. 
They  deem  it  impossible  to  think  of  any  way  in  which  such  neutraliza- 
tion could  occur,  as  the  amounts  of  acetonetrile  rendered  harmless  are 
so  out  of  proportion  with  the  amounts  of  thyroid  fed.  In  their  judg- 
ment the  thyroid  seems  to  alter  the  metabolism  in  such  a  way  that  the 
acetonetrile  is  disposed  of  without  breaking  down  into  its  poisonous 
constituents,  as  occurs  in  normal  glands. 

To  believe  that  acetonetrile  rendered  harmless  is  out  of  proportion 
to  the  amounts  of  thyroid  fed  is  no  argument  against  the  neutralization 
theory.  Most  probably  the  thyroid  hormones  do  not  differ  from  those 
of  other  organs.  We  know,  for  instance,  that  extremely  small  amounts 
of  adrenalin  are  capable  of  causing  the  most  energetic  and  powerful 
muscular  contractions,  the  effect  in  this  case  being  entirely  out  of  pro- 
portion to  the  cause.  We  know,  too,  that  very  small  amounts  of  secre- 
tin are  capable  of  causing  an  abundant  pancreatic  and  duodenal  secre- 
tion; that  all  diastases  contain  a  metal  or  metalloid  in  absolutely  impon- 


INTERRELATION  OF   THE  ORGANS  OF  INTERNAL  SECRETION     oo 

derable  proportions,  yet  absolutely  necessary  for  their  efficacy,  though 
entirely  out  of  proportion  to  their  effects.  To  be  sure,  arguments  are 
not  facts,  and  so  there  is  still  room  for  discussion. 

Were  there  a  direct  interaction  between  poisons  and  the  thyroid, 
the  same  results  should  be  expected  in  all  classes  of  animals.  Hunt  and 
Seidell  have  shown  that  if  the  thyroid  protects  mice  against  acetonetrile, 
on  the  other  hand  it  increases  the  suceptibihty  to  these  poisons  in  rats 
and  guinea-pigs.  If,  then,  the  thyroid  has  a  neutralizing  action,  why 
should  it  neutralize  in  the  one  case  and  not  in  the  other  ?  Therefore 
these  authors  conclude  that  when  an  unusual  poison,  such  as  acetonetrile, 
is  introduced  into  an  animal,  its  fate  will  depend  upon  how  the  animal's 
metabolism  concerning  this  poison  has  been  affected  by  the  thyroid. 
The  metabolism  of  mice  has  been  affected  in  such  a  way  that  acetonetrile 
is  rendered  harmless,  whereas  in  rats  and  guinea-pigs  it  becomes  harm- 
ful. What  occurs  to  acetonetrile  is  compared  by  Hunt  and  Seidell  to 
what  happens  to  methyl  and  ethyl  alcohol  (loc.  cit.):  "When  such  a 
poison  as  ethyl  alcohol  is  introduced  into  the  organism,  the  metabolism 
not  only  renders  it  harmless  but  makes  it  useful  for  the  body  in 
utilizing  the  energy  set  free.  In  the  case  of  methyl  alcohol,  although 
oxidation  may  proceed  along  similar  lines,  part  of  the  alcohol  is  con- 
verted into  poisonous  substances  (formaldehyde  and  formic  acid). 
The  fate  of  acetonetrile  in  the  body  of  the  mouse  must  be  compared  to 
the  fate  of  ethyl  alcohol,  and  the  fate  of  acetonetrile  in  the  body  of  the 
rat  which  has  been  fed  with  thyroid  to  that  of  methyl  alcohol."  Conse- 
quently, these  authors  and  others,  as  G.  Gauthier,  believe  that  the  thv- 
roid  gland  instead  of  neutralizing  the  toxic  products  of  metabolism  pre- 
vents their  formation.  It  has,  then,  a  regulating  action  on  the  nutritional 
exchanges. 

Functional  Interrelation  of  the  Organs  of  Internal  Secretion. — It  would 
be  a  mistake  to  believe  that  the  thyroid  is  left  entirely  to  its  own  resources 
in  its  gigantic  task,  the  regulation  of  the  metabolism.  It  receives 
material  support  from  other  organs.  For  instance,  the  suprarenal  bodies 
are  indispensable  to  life;  they  not  only  exert  an  antitoxic  action  over  a 
certain  number  of  poisons  circulating  in  the  blood,  as  the  one  resulting 
from  fatigue,  but  also  throw  into  the  blood  stream  substances  which 
regulate  the  function  of  the  vasomotors,  cardiac,  respiratory,  and 
muscular  centers.  The  hypophysis,  according  to  Guerrini,  Salvioli  and 
Carraro,  has,  too,  an  antitoxic  function  and  regulates  the  blood-pressure 
and  the  cardiac  rhythm.  Besides  its  digestive  function  the  pancreas 
influences  metabolism  in  regulating  the  production  and  absorption  <>t 
sugar.  Besides  their  known  physiological  action  the  genital  glands  secrete 
substances  which,  carried  into  the  blood,  have  a  favorable  action  over 
the  vitality  and   tonicity  of  the   muscular  system.     We  must   therefore 


56  BIOLOGICAL  CHEMISTRY 

consider  these  glands  with  internal  secretion  as  organs  whose  chief  duty 
is  to  regulate  metabolism.  They  seem  to  be  dependent  upon  one  another. 
If  one  of  these  organs  should  become  out  of  order,  then  more  or  less 
important  functional  disturbances  will  take  place  in  the  other  fellow- 
glands.  There  is  among  them  an  anatomical  and  functional  harmony, 
a  kind  of  biological  synergy,  through  which  the  functional  equilibrium 
is  maintained.  These  reciprocal,  functional  relations  have  been  estab- 
lished by  numerous  experiments.  After  thyroidectomy  an  hypertrophy 
of  the  hypophysis  takes  place;  in  myxedematous  patients  the  hypophysis 
has  been  found  to  be  increased  in  size,  as  a  rule.  After  thyroidectomy 
the  thymus  may  undergo  such  an  hypertrophy  as  to  cause  a  sudden 
tracheostenosis  and  death.  Revivescence  of  the  thymus  in  Basedow's 
disease  is  a  common  occurrence.  Cecca  showed  that  after  ovariectomy 
and  orchidectomy  an  hypertrophy  of  the  thyroid  and  suprarenal  bodies 
takes  place.  Tescione  came  to  the  same  results.  Pirera  and  Soraud 
believe  that  between  the  pancreas  and  thyroid  there  is  not  only  a  func- 
tional relation  but  also  a  sort  of  substitution.  They  found  that  when  the 
pancreas  had  been  removed  the  antitoxic  function  of  the  thyroid  was 
increased.  According  to  Eppinger,  Falta  and  Rudinger  there  exists  a 
reciprocal  inhibitory  action  between  the  pancreas  and  the  thyroid, 
between  the  pancreas  and  the  chromaffin  system,  while,  on  the  other 
hand,  between  the  thyroid  and  the  chromaffin  system  a  reciprocal, 
excitatory  action  is  found.  The  consequences  of  such  facts  are  easy  to 
foresee.  When  the  thyroid  is  removed,  its  inhibitory  action  over  the 
pancreas  having  ceased,  a  hyperfunction  of  that  organ  must  be 
expected;  but  as  its  excitatory  action  en  the  chromaffin  system  has 
disappeared,  the  function  of  the  latter  naturally  diminishes.  In  hyper- 
thyroidism the  inhibitory  action  on  the  pancreas  is  exaggerated  and  a 
relative  insufficiency  of  the  latter  organ  takes  place;  hence  the  intestinal 
disturbances  so  frequently  seen  in  that  condition.  On  the  other  hand, 
as  the  excitatory  action  over  the  chromaffin  system  is  increased  the 
latter  system  will  be  found  in  a  state  of  hyperfunction.  From  all  these 
extremely  interesting  facts  we  can  conclude  there  is  between  all  the 
organs  with  an  internal  secretion  a  functional  correlation,  a  sort  of 
physiological  team-work.  The  normal  function  of  one  organ  is  dependent 
to  a  certain  extent  upon  the  normal  function  of  the  others,  and  when 
one  is  out  of  order  it  cannot  fail  to  have  a  pathological  repercussion  on 
the  others.  Endocrinology  is  a  science  still  in  its  infancy,  but  its 
promises  are  far-reaching;  if  fulfilled,  it  will  be  one  of  the  richest  fields 
to  harvest. 


CHAPTER   IV. 
PATHOLOGY. 

Synonyms  in  Latin:  Struma;  guttur  turgidum.  French:  Goitre;  gros 
cou.  German:  Kropf;  Blaehals.  Italian:  Gozzo.  Spanish:  Papera. 
English:  Goiter;  great  neck. 

According  to  Virchow  a  goiter  is  only  the  continuation  of  the  natural 
development  of  the  thyroid  gland.  In  a  follicle,  cellular  proliferation 
takes  place  by  division  of  the  cells,  which  gradually  form  solid  papillary 
formations  bulging  in  the  interior  of  the  follicle  and  filling  the  follicular 
lumen.  Interstitial  connective  tissue  penetrates  these  papillary  forma- 
tions, carrying  with  it  their  vascular  supply.  Gradually  they  shape 
themselves  into  a  more  or  less  follicular  form.  In  this,  colloid  secretion 
appears;  hence  the  follicle;  hence  the  goiter. 

If  this  process  is  localized  to  a  part  of  the  gland,  then  we  have  a 
nodular  goiter;  but  if  this  process  takes  place  all  over  the  gland,  then  we 
have  a  diffuse  goiter.  Such  goiter  may  become  later  on  a  cystic,  fibrous, 
or  a  calcareous  goiter;  this  depends,  however,  upon  the  secondary  degen- 
erative changes  which  will  take  place  in  it.  In  conclusion,  according  to 
\  irehow,  a  goiter  originates  bv  the  subdivision  of  adult  folhcuh  into 
smaller  ones;  these  in  turn  proliferate  and  finally  form  other  adult 
alveoli.     Hitzig,  in  1894,  shared  the  same  view. 

In  1893  Wolfler  modified  Virchow's  conception  as  to  the  origin  of 
goiter.  Contrary  to  Virchow's  theory,  which  claims  that  goiter  is  due 
to  hyperplasia,  \\  olfler  claims  that  it  is  due  to  neoplasia:  that  it  is  the 
consequence  of  the  proliferation  of  the  embryonic  epithelium,  remaining 
between  adult  alveoli,  and  which  is  found  mostly  in  the  cortical  zone  of 
the  gland.  These  embryonic  cellular  residues,  according  to  Wolfler's 
theory,  are  the  ones  which  at  one  time  or  another  may  begin  to  prolif- 
erate and  form  goiter,  which  Wolfler  calls  adenoma. 

In  his  judgment  an  adenoma  is  an  epithelial  tumor  with  atypical 
vascularization,  developed  from  embryonic  glandular  residues.  It  m 
the  proliferating  process  the  epithelium  keeps  its  embryological  aspect, 
the  consequence  of  it  is  a  fetal  adenoma;  but  if  the  epithelium  tends 
gradually  toward  the  adult  aspect,  it  then  gives  rise  to  a  parenchymatous 
and  colloid  goiter.  Wolfler  distinguishes  two  kinds  of  adenoma,  the 
benign  and  malignant. 

I  hese  two  theories,  although  extremely  interesting  and  partly  cor- 


58  PATHOLOGY 

rect,  do  not  explain  satisfactorily  the  origin  of  all  the  tumors  found  in 
the  thyroid  gland;  for  instance,  they  do  not  explain  the  origin  of  goiters 
with  squamous  epithelium,  and  they  do  not  take  into  consideration  at 
all  a  number  of  tumors  found  in  the  thyroid  gland  which  have,  as  we 
will  see  later  on,  a  very  different  origin.  I  refer  to  tumors  developed 
from  the  thyroglossus  duct;  from  the  parathyroid;  from  the  postbranchial 
bodies,  etc. 

In  the  last  few  years  the  study  of  the  embryology  of  the  thyroid 
has  afforded  more  light  on  the  obscure  field  of  its  pathology.  This  has 
been  true,  too,  of  the  ovary,  testicle,  and  kidney.  We  might  say  there  is 
a  peculiar  analogy  between  tumors  developed  in  these  organs  and  those 
developed  in  the  thyroid.  Tumors  developed  in  the  parathyroid  and 
called  parastruma  are  analogous  to  renal  tumors  called  hypernephroma, 
and  which  are  developed  from  the  suprarenal  bodies.  Tumors  with 
cylindrical  epithelium  originating  from  the  thyroglossus  duct  find  their 
analogy  in  tumors  developed  in  Wolfs  canal.  Mixed  tumors  of  the 
thyroid  originating  from  the  branchial  bodies  find  their  analogy  in  the 
mixed  tumors  of  the  kidney  originating  from  the  primitive  sclero- 
myotomata.  Langhans,  of  Berne,  and  his  pupils,  Michaud,  Verebely  and 
Getzowa,  are  entitled  to  a  great  deal  of  credit  for  attempting  to  clear 
up  this  question  of  the  origin  of  thyroid  tumors.  Lately  De  Quervain, 
in  1909,  and  Berard  and  Alamartine,  in  191 2,  took  up  this  subject, 
looking  at  it  from  an  embryological  point  of  view. 

We  call  goiter  any  enlargement  of  the  thyroid  gland.  If  this  enlarge- 
ment shows  clinically  and  pathologically  the  characteristics  which  we 
attribute  to  benign  tumors,  then  it  is  called  benign  goiter;  otherwise  we 
call  it  malignant  goiter.  If  vascular  symptoms  and  congestion  are  the 
predominating  features,  then  we  regard  it  as  a  vascular  goiter.  If  infec- 
tion sets  in  in  a  preexisting  goiter,  we  call  it  strumitis;  but  if  infection 
affects  a  normal  thyroid,  we  call  it  thyroiditis. 

The  enlargement  may  affect  only  a  part  of  the  gland  or  the  gland 
in  toto.  If  the  goiter  is  made  up  of  one  or  several  nodules,  we  call  it 
nodular  goiter.  If  the  enlargement  is  diffusely  distributed  throughout 
the  gland,  we  call  it  diffuse  goiter.  We  may  have  a  diffuse  parenchyma- 
tous goiter  or  a  diffuse  colloid  goiter,  according  to  the  nature  of  the 
thyroid  degeneration. 

In  nodular  goiter  proliferation  and  the  distribution  of  follicles  are 
very  much  more  irregular  and  unequal.  The  nodular  goiter  is  usually 
colloid  or  cystic,  and  has  a  greater  tendency  to  undergo  hyalin,  fibrous, 
calcareous  metamorphosis.  Hemorrhage  takes  place  more  frequently 
in  nodular  than  in  diffuse  goiter.  The  nodular  goiter  is  more  common  in 
the  lower  pole  of  the  gland.  It  is  oftentimes  multiple  and  seldom  develops 
in  the  pyramidal  process. 


PATHOLOGY 


59 


A  satisfactory  clinical  classification  of  the  thyroid  tumors  is  not  easy 
on  account  of  the  difficult}*  of  bringing  into  harmony  the  clinical  with 
the  pathological  facts.  The  classification  based  on  embryology  alone  is 
extremely  interesting  and  scientific,  but  clinically  it  is  confusing,  as  it 
mixes  up  in  the  same  chapter  the  benign  and  malignant  forms  of  goiter, 
which,  clinically,  are  so  different.  Therefore,  I  think  that  until  we  have 
something  better  the  following  classification  will  answer  the  purpose: 


I.   Parenchymatous  goiter. 

II.  Colloid. 
III.   Fetal  adenoma. 

I.  Epithelial  tumors. 


Pubertv. 
Pregnancv. 


II.  Connective-tissue  tumors. 


III.  Mixed  tumors. 

IV.  Dermoids,  Teratoma. 


V.  A 


ccessory  goiters. 


Benign  Tumors. 

I.   Physiological 

|   2.  Non-toxic. 
I   3.    1  hyrotoxic. 
I  Cystic. 
j   Fibrous. 

Calcareous. 

Osseous. 


Malignant  Tumors. 

1.  Malignant  adenoma  or  proliferating  goiter. 

2.  Carcinoma. 

3.  Metastatic  colloid  goiter. 
•I  4.  Parastruma. 

5.  Postbranchial  goiter. 

6.  Papilloma. 

7.  Cancroid. 

1.  Fibrosarcoma. 

2.  Polymorphous-cell  sarcoma. 

3.  Round-cell  sarcoma. 

4.  Myxosarcoma. 

5.  Endothelioma. 

6.  Perithelioma. 


Median  cysts. 
Lingual  goiter. 
Intratracheal  goiter. 

Intrathoracic  accessory  goiter. 
( )\  arian  goiter. 


Inflamma  I  tONS. 


Acute 


I.  Bacterial. 

II.  Toxic. 

III.    Parasitical 


j  Non-purulent 


Purulent. 

Syphilis. 

Clironic  I  uberculosis. 

\\  oody  1  In  roiditis. 

I  1  h\  roiditis. 

Echinococcus. 


60 


PATHOLOGY 


BENIGN    TUMORS. 

Parenchymatous  Goiter. — This  type  of  goiter  is  formed  by  glandular 
proliferation.  It  is  associated  with  metabolic  disturbances,  with  puberty, 
menstruation,  pregnancy,  lactation,  and  the  menopause.  Nothing  is 
known  definitely  regarding  the  cause  of  thyroid  hyperplasia  at  these 
periods. 

Diffuse  enlargement  of  the  thyroid  gland,  non-toxic  in  nature  is 
often  observed.  It  is  then  known  as  the  non-toxic  parenchymatous 
goiter  (Fig.  9).  When  toxic  symptoms  are  present,  we  call  it  thyrotoxic 
parenchymatous  goiter.  This  latter  form  will  be  studied  in  the  chapter 
on  Exophthalmic  Goiter. 


Q 

D 


% 


Q 


Fig.  9. — Non-toxic  parenchymatous  goiter.      X  S3- 


Histologically,  the  physiological  and  non-toxic  parenchymatous  goiter 
is  characterized  by  an  enlargement  of  all  the  glandular  elements.  The 
number  of  follicles  is  increased  and  they  are  slightly  increased  in 
size.  They  may  contain  colloid  in  slightly  larger  quantities  than  nor- 
mally, or  they  may  not.  The  colloid  is  rich  in  iodin.  The  number  of 
cells  shows  an  increase  in  size  and  number  also.  The  interfollicular 
connective  tissue  may  be  normally  developed  or  slightly  increased.  Its 
cut  surface  is  slightly  granular  as  the  consequence  of  the  increase  in  the 
size  of  the  follicles  and  their  bulging  out.  The  consistency  is  firm. 
Iodin  generally  has  a  marked  therapeutic  effect  on  this  form  of  goiter. 


PLATE  I 


Colloid  Goiter.      X  40. 


FIG.  2 


Wolfler's  Fetal   Adenoma.      X  lOO. 
With  intrafollicular  hemorrhages. 


BEXIGX   TUMORS  61 

The  histological  picture  of  the  goiter  taken  altogether  is  a  picture 
of  a  more  or  less  normal  gland  in  which  all  the  elements  show  an  increase 
in  size  and  number,  but  in  which  the  different  elements  have  kept  more 
or  less  their  natural  relations,  one  to  another. 

Colloid  Goiter. — Its  main  characteristic  is  the  increased  quantity  of 
colloid.  This  colloid  is  generally  thick,  staining  readily.  It  contains 
fewer  vacuoles  than  normally,  and  completely  fills  the  follicle.  Its 
iodin  content  is  diminished. 

The  follicles  have  lost  their  normal  proportions  and  show  all  kinds 
of  form  and  size.  (Plate  I,  Fig.  i.)  The  epithelium  is  low  or  flat;  blood 
supplv  of  the  colloid  goiter  is  diminished,  and  the  interfollicular  stroma 
is  more  or  less  abundant,  showing,  as  a  rule,  extensive  hyalin  degenera- 
tion (Fig.  10). 


Fig.   io. — Hyalin  degeneration  and  increased  connective  tissue  of  a  goiter.     First  step 
toward  formation  of  a  fibrous  goiter.      X  40. 

If  the  colloid  degeneration  does  not  affect  the  diffuse  type,  but  is 
nodular,  the  surface  of  the  goiter  is  then  coarsely  lobulated.  1  he  con- 
sistency may  be  harder  or  softer  than  in  parenchymatous  goiter,  and  the 
cut  surface,  more  or  less  irregularly  lobulated,  shows  a  thick,  tenacious, 
transparent  material  which  is  colloid.  Its  color  depends  upon  its  con- 
tent of  hemorrhagic  blood. 

It  would  be  erroneous  to  believe  that  even  in  a  diffuse  colloid  goiter 
every  follicle  has  undergone  colloid  degeneration.  Between  the  degen- 
erated follicles  there  is  always  a  number  of  normal  vesicles  and  non- 
differentiated  cellular  masses  of  embryonic  type,  which  will  proliferate 
and  form  new  alveoli  in  order  to  take  up  the  lost  or  diminished  function 
of  the  degenerated  follicles. 


62 


PATHOLOGY 


Colloid  degeneration  may  affect  the  entire  gland  and  give  rise  to  a 

diffuse  colloid  goiter,  or,  localized  to  a  small  portion  of  the  thyroid,  may 

form  a  nodular  colloid  goiter.     Colloid  nodules  may  be  singles  or  multiples. 

The  colloid  goiter  may  give  rise  to  a  cyst.     There  are  two  kinds  of 

cyst,  the  true,  and  the  false. 

The  true  cyst  is  of  follicular  origin.  Two  or  more  follicles  become 
distended  by  the  colloid  secretion,  and  as  a  consequence  of  the  continued 
eccentric  pressure  on  their  follicular  walls  the  blood  supply  is  slowly 
cut  off,  the  alveolar  walls  undergo  atrophy,  and  finally  break  and  fuse 
together,  forming  a  larger  space  filled  with  colloid  (Fig.  u).     The  cyst 

is  formed.  It  increases  gradually  in  size, 
takes  up  a  round  form,  and  presses  toward 
the  periphery  of  the  surrounding  follicles, 
which  owing  to  the  continuous  pressure, 
undergo  a  connective-tissue  degeneration 
and  fuse  with  the  true  or  follicular  capsule 
of  the  cyst,  thus  forming  a  thick,  cystic 
capsule.  A  cyst  may,  furthermore,  take  its 
origin  from  an  intrafollicular  hemorrhage. 

The  false  cyst  is  the  consequence  of  a 
hemorrhage  which  dissociates  the  stroma 
of  the  gland  and  causes  a  necrotic,  aseptic 
area.  If  the  hemorrhage  is  of  small  size, 
it  gradually  becomes  absorbed.  Pigmen- 
tation remains  for  a  long  time  as  the  only 
proof  of  the  bloody  extravasation.  But  if 
the  hemorrhage  is  of  some  consequence, 
the  hemorrhagic  focus  being  too  large  to 
become  absorbed,  a  localized,  aseptic 
Fig.  ii.— Walls  between  large     neCrosis   takes    place   and    the   neighboring 

colloid    alveoli    become    atrophied        •  i       •      *.  iy„  ni.n    f„^^,:„„  ^  f0lPQ 

_j  /  tissues  begin  to  proliferate,  forming  a  raise 

capsule  around  this  hemorrhage;  hence  the 

formation  of  an  encapsulated  cyst. 

The  size  of  a  true  cyst  may  become  enormous.  As  the  ovarian  cyst 
it  may  be  mono-  or  multilocular  and  may  contain  a  serous,  transparent 
fluid,  which  may  be  red  if  a  recent  hemorrhage  has  taken  place,  or  it 
may  be  of  chocolate-brown  color  if  the  hemorrhage  is  older.  The  hemor- 
rhage is  the  result  of  a  rupture  of  one  or  more  small  bloodvessels  of  the 
wall  of  the  cyst,  as  a  consequence  of  the  chronic  endarteritis,  or  of 
atrophic  changes  resulting  from  mechanical  pressure.  Crystals  of 
cholesterin  are  often  found,  especially  in  the  serous  form. 

The  walls  of  the  cyst  may  be  thick  or  rigid,  or  may  be  thin  and 
soft.     The  inner  surface  mav  be  smooth  or,  as  in  the  ovarian  cyst,  may 


and    give  rise  to  a  cystic  forma 
tion.      X  21 


BEXIGX   TUMORS 


63 


be  covered  with  papillary  formations.  It  is  lined  with  epithelium 
derived  from  the  follicles,  while  there  is  no  epithelial  lining  in  the  false 
cysts  of  hemorrhagic  origin.  The  walls  of  the  cysts  may  show  calcareous 
deposits. 

In  both  forms  of  goiter,  colloid  and  parenchymatous,  vascular 
changes  may  become  so  prominent  that  the  arteries  and  veins  are  con- 
siderably increased  in  size  and  number.  In  such  cases  an  expansive 
pulsation  is  present  all  over  the  goiter;  a  thrill  is  felt  on  the  main  trunks 
of  the  arteries;  a  systolic  murmur  is  heard  all  over  the  gland.  This 
form  is  called,  clinically,  vascular  goiter.  It  is  usually  found  in  connec- 
tion with  exophthalmic  goiter;  this  vascular  goiter,  however,  may  be 
observed  in  cases  in  which  no  thyrotoxic  symptoms  whatsoever  are 
present.     It  is  then  known  as  the  non-toxic  vascular  goiter. 


FlG.   12. — Pure  fibroma  encapsulated  in  a  colloid  goiter.      X  9. 


Both  forms  of  goiter  may  undergo  amyloid  degeneration,  but  this  is  rare. 

As  a  result  of  chronic  irritation  or  inflammation,  connective  tissue 
may  develop  secondarily  in  a  parenchymatous  or  colloid  goiter  and 
thus  form  a  fibrous  goiter  (Fig.  12).  Histologically,  this  is  not  a  new 
form  of  goiter,  but  only  the  result  of  a  secondary  degeneration.  The 
same  is  true  of  the  calcareous  deposits  which  oftentimes  take  place  in 
goiter,  and  which  may  convert  a  nodular  colloid  goiter  into  a  hard, 
calcareous  lump.  Such  conditions  should  be  considered  as  secondary 
degenerative  changes  and  should  not  be  regarded  as  pathological  entities 
In    themselves. 


64 


PATHOLOGY 


I  Fetal  Adenoma. — This  form  of  goiter  is  called  fetal  adenoma  because 
it  is  formed  from  embryonic  tissue,  because  it  is  of  congenital  origin, 


...Vs' 


Wi 


i»W, 


0 


M   1% 


Fig.   13. — Wolfler's  fetal  adenoma.      X  90. 


*> 

.  #**.■  ■■ 

'£#• 

■  ,<» 

*■? 

•  * 

St 

&*}\ 

1  mM 

&§ 

*<*. 

t  *  *  A 

it! 


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Fig.   14. — Wolfler's  fetal  adenoma.      Alveoli  show  a  tendency  toward  the  colloid  type. 

X  100. 

and  because  the  normal  parenchyma  of  the  gland  does  not  take  any 
part  in  its  formation. 


MALIGNANT  GOITERS  65 

The  fetal  adenoma  develops  in  the  early  part  of  life,  but  is  more 
common  at  the  time  of  puberty.  It  seldom  exceeds  the  size  of  a  lemon, 
but,  as  a  rule,  the  adenomata  are  multiple  and  may  reach  twentv  or 
more  in  number.  If  in  a  young  individual  from  ten  to  twentv  vears 
old,  several  small,  round,  mobile,  painless  nodules  with  sharp  limits  and 
firm  consistency  are  found,  one  can  be  almost  sure  that  they  are  fetal 
adenomata.  Such  goiters  generally  do  not  give  rise  to  symptoms 
except  when  numerous  and  large  in  size;  they  may  then  cause  pressure 
symptoms. 

Histologically,  this  goiter  is  formed  from  embryonic  cells  and  embry- 
onic follicles.  The  follicles  are  small  and  the  cells  which  line  their  walls 
have  a  fetal  character.  (Fig.  13,  and  Plate  I,  Fig.  2.)  They  are  of 
medium  size  and  stain  intensely.  The  follicles  have  a  very  small  diam- 
eter and  are  uniformly  of  about  the  same  size.  The  lumen  in  the  early 
stage  does  not  contain  any  colloid,  but  may  do  so  later  (Fig.  14);  in 
further  development  it  may  be  converted  into  a  colloid  goiter.  The 
interfollicular  connective  tissue  is  very  abundant  and  seems  to  have  a 
mucoid  aspect. 

These  different  forms  and  varieties  of  goiters  are  not  found,  as  a 
rule,  so  clearly  defined  and  separated  in  a  goiter  as  I  have  described 
them.  Usually,  they  are  mixed  together,  one  form  predominating  more 
than  the  other,  and  it  is  this  feature  which  gives  to  a  goiter  such  a 
polymorphic,  histological  aspect. 

MALIGNANT    GOITERS. 

We  distinguish  tumors  developed  from  the  epithelium  and  tumors 
developed  from  the  connective  tissue  of  the  thyroid  gland.  To  the  first 
class  belong  the  epithelial  neoplasms  and  to  the  second,  the  connective- 
tissue  tumors  or  sarcomata. 

One  of  the  chief  characteristics  of  a  malignant  goiter  is  its  tendency 
to  metastasis. 

Metastases  of  malignant  goiter,  whether  of  epithelial  or  connective- 
tissue  origin,  may  take  place  through  the  lymphatics  or  through  the 
bloodvessels.  The  general  formula  applied  to  malignant  tumors  when 
speaking  about  their  mode  of  dissemination:  "Hematogenous  route  for 
sarcomata,  lymphatic  route  for  cancerous  tumors,"  does  not  hold  good 
any  longer  here. 

Metastases  of  epithelial  malignant  goiters  occur  more  frequently  in 
bones  than  metastases  of  sarcomata.  In  both  varieties,  metastases  in 
the  lungs  are  very  frequent. 

In  going  over  statistics  of  cancer  in  general  it  has  been  found  that 
cancer  of  the  thyroid  occupies  the  most  prominent  place-  so  far  as  metas- 


6(3  PATHOLOGY 

tases  in  bones  are  concerned;  then  comes  the  cancer  of  the  prostate. 
Hassner,  for  instance,  finds  that  in  140  cases  of  cancer  of  the  thyroid 
there  were  34  cases  of  metastases  in  bones,  making  24.3  per  cent.;  in 
1358  cases  of  cancer  of  the  breast,  only  106  metastases  in  bones,  making 
7.8  per  cent.;  in  203  cases  of  cancer  of  the  uterus,  7  cases  of  metastases 
in  bones,  making  3.4  per  cent.;  in  247  cases  of  cancer  of  the  kidney,  9 
cases  of  metastases  in  bones,  making  3.7  per  cent.;  while  in  903  cases 
of  cancer  of  the  stomach  not  a  single  metastasis  in  the  skeleton  was 
found. 

Metastases  of  malignant  thyroid  tumors  show  a  marked  predilec- 
tion first  of  all  for  the  skull,  then  comes  the  pelvis,  sternum,  femur, 
clavicle,  lower  jaw,  and  the  shoulder-blade.  Metastases  in  bones,  as  a 
rule,  are  not  multiple. 

Recklinghausen,  trying  to  explain  the  reason  why  bony  metastases 
of  malignant  tumors  of  the  thyroid  were  so  frequent,  thought  that  in 
bones,  on  account  of  the  sudden  widening  of  the  venous  spaces,  the 
blood  stream  takes  a  slower  course,  thus  offering  the  possibility  and 
time  to  cancerous  cells  to  become  permanently  settled  and  then  to 
grow.  That  may  be  so,  but  this  theory  does  not  explain  why  cancers 
of  the  thyroid  are  the  ones  which  develop  metastases  in  bones  much 
more  frequently  than  cancers  of  the  other  organs  of  the  body. 

One  peculiarity  of  these  malignant  metastases  is  their  ability  to 
revert  to  the  normal  type  of  thyroid  tissue;  in  other  words,  if  a  micro- 
scopic examination  of  such  metastases  is  made  the  malignant  character 
of  the  tumor  may  have  disappeared  entirely,  or  have  diminished  to 
such  an  extent  that  the  microscopic  picture  is  mostly  one  of  normal 
glandular  structure.  Cramer  explains  this  by  saying  that  in  metastases 
few  cells,  partly  malignant  and  partly  normal,  are  carried  away  into 
the  blood  stream,  and  that  cancerous  cells,  being  more  resistant  than  the 
normal  ones,  grow  first,  and  only  then  under  their  protectorate  normal 
cells  proliferate,  outgrowing  later  on  the  cancerous  ones.  "Se  non  e 
vero  e  ben  trovato." 

Meyer-Hurlimann  and  Ad.  Oswald  had  the  opportunity  to  observe 
a  remarkable  case  of  cancer  of  the  thyroid.  After  *-ray  treatment  the 
tumor  softened  and  began  to  secrete  an  enormous  amount  of  a  serous, 
brownish-yellow  fluid  which  chemically  and  physiologically  showed  the 
same  properties  as  normal  thyroid  secretion.  This  shows  that  malig- 
nant degeneration  of  the  thyroid  does  not  deprive  the  latter  organ  of  its 
normal  function. 

The  faculty  of  these  cells  not  only  to  shape  themselves  into  normal 
alveoli,  but  also  to  secrete  colloid,  raises  one  of  the  most  interesting 
problems  of  ontology  and  teleology.  How  is  it  that  malignant  cells  which 
cannot  be  differentiated  from  normal  ones  will  be  carried  away  by  the 


PLATE  II 


Malignant  Adenoma. 

Large    vascular    lacunary    formations    cut    transversely    and    surrounded    by    cellular 
masses.     This   picture   is   typical   too   for  the   malignant   adenoma.      X  50. 


Malignant    Adenoma. 

Capillary  vessels  are  formed  by  an  endothelial  wall  without  adventitia.  Note  their 
lacunary  forms.  Note  in  a  the  close  relation  between  the  tumor  cells  and  the 
endothelium.      X  280. 


MALIGNANT  GOITERS  67 

blood  stream,  and  will  not  only  grow  upon  a  strange  land  but  will  also 
not  be  deprived  of  their  physiological  action  which  is  the  colloid  secre- 
tion ?  A  similar  feature  does  not  occur  in  cancerous  metastases  of  other 
organs.  Metastases  of  the  breast  do  not  secrete  milk,  nor  does  a  metas- 
tasis of  the  liver  secrete  bile,  nor  does  a  metastasis  of  the  cancerous 
kidney  secrete  urine.     Who  can  give  the  answer  ? 

That  such  metastases  are  capable  of  normal  physiological  function 
is  a  very  well-known  fact.  Classical  is  the  case  of  von  Eiselsberg  who 
performed  a  complete  thyroidectomy  for  a  malignant  tumor.  Nothing 
worth  notice  followed  the  operation,  but  later  on,  when  in  a  subsequent 
operation  a  metastasis  was  removed,  marked  symptoms  of  myxedema 
soon  developed. 

Malignant  tumors  of  the  thyroid  seem  to  have  a  peculiar  tendency 
to  penetrate  the  walls  of  the  veins  even  in  the  early  stage  of  their  growth, 
and  it  is  not  uncommon  indeed,  at  operations  of  cases  which  clinically 
seem  to  be  most  favorable,  to  find  the  thyroid  imae  veins  thrombosed 
and  already  invaded  by  the  tumor. 

It  is  to  the  Bernese  pathologists,  Langhans  and  his  pupils,  that  we 
are  really  indebted  for  what  we  know  of  the  malignant  epithelial  tumors 
of  the  thyroid.  Their  classification  is  based  upon  the  fact  that  embryo- 
logical  remnants  of  various  organs  may  remain  included  in  the  thyroid 
gland  and  give  rise  to  tumor  at  one  time  or  another. 

1.  Malignant  adenoma  or  proliferating  goiter. 

2.  Carcinoma. 

3.  Metastatic  colloid  goiter. 
Epithelial  tumors.                    \  4.  Parastruma. 

5.  Postbranchial  goiter. 

6.  Papilloma. 

7.  Cancroid. 

Malignant  Adenoma  or  Proliferating  Goiter. — This  has  been  called 
adenocarcinoma  by  von  Eiselsberg  and  malignant  adenoma  by  Kocher. 
The  denomination,  proliferating  goiter,  applied  to  that  form  of  tumor 
might  be  confused  with  the  hyperplastic  goiter  which  is  not  malignant. 
Therefore  I  prefer,  especially  from  a  clinical  point  of  view,  to  adopt 
the  denomination  of  Kocher:  malignant  adenoma. 

Macroscopically,  it  is  represented  by  a  single  nodule  or  growth  of  a 
diameter  ranging  from  10  to  15  cms.;  it  is  seldom  larger.  I  have,  how- 
ever, operated  recently  a  malignant  adenoma,  involving  both  lobes  and 
isthmus,  very  vascular,  each  lobe  measuring  about  20  x  15  x  10  cms. 
Occasionally  the  tumor  may  be  formed  bv  more  than  one  nodule.  Its 
surface  is  lobulated  and  the  capsule  is  more  or  less  thick.  Inwardly, 
septa  divide  the  parenchyma  into  lobi  and  lobuli,  while  in  or  near  the 


68 


PATHOLOGY 


center  of  the  nodule  there  is  a  more  or  less  constantly  necrotic  area 
giving  the  tissue  a  scar-like  appearance.  The  cut  surface  is  like  marrow, 
of  a  grayish-white  color,  and  more  or  less  cloudy  juice  can  be  expressed. 
Microscopically,  the  tumor  is  formed  by  regular,  polyhedric  lobuli  with 
round  corners,  resembling  very  much  normal  enlarged  follicles  (Fig.  15). 
Between  them  are  found  capillaries  composed  merely  of  an  endothelial 
wall,  with  no  adventitia,  and  with  no  muscular  and  elastic  fibers  (Fig. 
16).    Affecting  a  lacunary  form  (Plate  II,  Fig.  1)  instead  of  a  round  shape, 


Cabsul< 


Fig.  15. — Malignant  adenoma.  Periphery  of  the  tumor.  Above,  capsule  infiltrated 
with  malignant  cells;  below,  large  polyhedric  fields  of  cells,  forming  solid  cellular  masses 
separated  by  trabecules  of  connective  tissue.      X  50. 


as  ordinary  capillaries  do,  they  lie  in  direct  contact  with  the  tumor 
cells.  (Plate  II,  Fig.  2.)  In  some  instances  they  surround  the  lobuli 
entirely,  forming  then  what  Minot  called  "sinusoid." 

The  above  microscopic  picture  found  even  in  a  very  small  particle  of 
a  tumor  or  of  a  metastasis  is  pathognomonic  for  the  malignant  adenoma 
or  proliferating  goiter. 

Cells  have  a  polyhedric  form,  and  at  the  periphery  of  the  nodule 
they  are  better  nourished  and  younger  than  in  the  center.  Their  pro- 
toplasm is  finely  granular  and  their  nuclei  are  round  or  oval,  measuring 
from  6  to  10  m.     Most  of  them  contain  one  or  more  nucleoles. 


MALIGNANT  GOITERS 


69 


In  places,  small  foci  of  undifferentiated  cells  gradually  shape  them- 
selves into  the  form  of  a  circle  in  which  colloid  appears,  thus  form- 
ing a  new  vesicle.  These  neoformed  vesicles,  when  considerable  in 
number  and  seen  at  a  lower  power,  give  to  the  field  a  peculiar,  screen- 
like appearance,  characteristic,  too,  of  the  proliferating  goiter  or  malig- 
nant adenoma.  Since,  later,  connective  tissue  appears  between  these 
vesicles,  this  neoformed  tissue  has  a  great  similitude  with  a  normal 
thyroid  gland.  The  scar-like  tissue  found  in  the  center  of  the  tumor  is 
formed  of  newly  organized  connective  tissue;  it  is  a  product  of  necrosis. 

Metastases  take  place  preferably  in  the  cranium  and  lungs,  through 
the  bloodvessels;  lymphatic  glands  are  not  involved. 


Fig.  16. — Malignant  adenoma.  Septa  between  the  lobuli.  They  are  formed  by  capil- 
lary vessels.  Note  lengthened  form  of  cellular  fields.  This  feature  is  very  characteristic 
of  malignant  adenoma.      X  50. 


Histologically,  the  malignant  adenoma  differs  entirely  from  the  ordi- 
nary cancer.  There  we  have  not,  as  in  cancer,  irregular  epithelial  masses 
surrounded  by  more  or  less  developed  and  irregularly  shaped  frame  of 
connective  tissue.  As  Langhans  says,  this  tumor  with  its  peculiar  for- 
mation, with  its  neoformed  vesicles  lined  with  one  layer  of  epithelium 
and  containing  colloid,  with  the  peculiar  shape  of  its  bloodvessels,  with 
the  irregularity  of  their  disposition,  of  the  construction  of  their  walls, 
and  their  intimate  relation  to  the  epithelium,  recalls  rather  a  normal 
organ  in  the  course  of  development  than  a  cancer.  Hence  the  name 
proliferating  goiter  given  by  Langhans. 


70  PATHOLOGY 

Does  the  malignant  adenoma  develop  from  goiterous  elements 
themselves  or  does  it  develop  from  embryonic  rests  of  undifferentiated 
normal  thvroid  tissue  ?  Langhans  thinks  that  the  second  alternative  is 
likely  to  be  true. 

Carcinoma. — The  cancer  of  the  thyroid  is  a  hard,  nodular  tumor,  as 
a  rule,  firmly  adherent  to  the  neighboring  tissues.  The  cut  surface  is  of 
grayish  white.  Typical  cancer  juice  can  be  expressed.  This  carcinoma 
has  a  tendency  to  undergo  softening  of  its  constituent  parts. 

Histologically,  this  cancer  shows  the  usual  microscopic  picture  which 
is  found  in  cancer  of  the  breast,  stomach,  etc.,  namely,  the  same  inter- 
relations between  connective  tissue  and  epithelium  which  enable  us  to 
diagnose  cancer.  Here,  too,  as  in  cancer  of  other  epithelial  organs,  we 
have  cellular  masses  irregularly  disposed,  surrounded  by  an  irregularly 
developed  stroma.  The  cancer  cells,  in  opposition  to  the  normal  cells 
of  the  thyroid,  have  a  poorly  developed  protoplasm;  they  are  small; 
their  nuclei  are  larger  than  those  of  a  normal  gland  and  measure  from 
10  to  i6m. 

In  cancer  of  the 'thyroid,  metastases  may  take  place  in  the  sternum, 
ribs,  pleura,  kidneys,  and  in  the  suprarenal  bodies.  The  cancer  does 
not  penetrate  the  bloodvessels  like  the  malignant  adenoma;  metastases 
occur  through  the  lymphatic  route:  hence,  involvement  of  the  cervical 
and  possibly  of  the  mediastinal  lymph  nodes. 

It  is  not  always  easy  to  decide  microscopically  if  a  metastasis  comes 
from  a  cancer  of  the  thyroid  or  not.  If  in  the  metastasis  vesicles  con- 
taining colloid  are  found,  the  diagnosis  is  easy.  If  not,  the  size  of  the 
cells  and  their  nuclei,  their  number  and  their  close  relation  one  to  another 
will  arouse  a  strong  suspicion  in  favor  of  their  thyroidal  origin. 

Metastatic  Colloid  Goiter. — Metastatic  colloid  goiter,  histologically, 
does  not  differ  in  any  way  from  a  simple  colloid  goiter.  There  is  nothing 
in  its  histological  picture  to  arouse  the  suspicion  of  malignancy.  In  the 
metastatic  as  well  as  in  the  primary  tumor  we  find  follicles  of  different 
forms,  round,  oval  or  elongated.  The  epithelium  of  such  vesicles  may  be 
cuboidal  or  cylindrical.  The  colloid  material  is  as  abundant  and  has 
the  same  tingible  power  as  the  colloid  of  a  simple  goiter.  It  may  be 
strongly  colored  by  the  eosin  or  its  coloring  power  may  be  diminished 
or  totally  absent.  Lymphatics  and  bloodvessels  are  normal  and  do  not 
contain  metastatic  cells.  The  capsule  of  the  nodule  is  absolutely  intact. 
The  only  feature  is  its  metastasizing  power. 

Metastases  in  the  great  majority  of  cases  take  place  through  the 
vascular  route;  they  may,  however,  occur  through  the  lymphatics.  In 
that  case  metastases  are  found  in  the  cervical,  mediastinal,  and  bronchial 
lymphatic  glands.  But  the  seat  of  predilection  of  such  metastases  is  in 
the  spinal  column,  sternum,  ribs,  and  long  bones. 


MALIGNANT  GOITERS  71 

Tumors  of  bones  due  to  metastatic  colloid  goiter  form  an  interesting 
pathological  chapter.  Clinically,  their  true  origin  is  not  recognized. 
Thev  are  considered  as  sarcomata,  and  it  is  only  at  the  microscopic  exam- 
ination that  the  error  is  discovered.  Cohnheim,  who  was  the  first  to 
report  a  case  of  metastatic  colloid  goiter  in  bones,  considers  these  tumors 
as  benign;  but  Recklinghausen  and  Wolfler  do  not  share  the  same  view 
and  consider  them  as  malignant,  claiming  that  a  tumor  which  is  capable 
of  giving  rise  to  metastases  is  not  entitled  to  the  denomination  of  benign 
tumor.  In  Wolfler's  judgment  this  metastatic  tendency  indicates  an 
increased  proliferative  energy,  which  is  one  of  the  chief  characteristics 
of  malignant  tumors.  Despite  the  authority  of  such  men,  Bontsch, 
Honsell,  Oderfeld,  von  Steinhaus,  Karl  Schmidt,  Patel,  etc.,  have  taken 
exception  to  such  conclusions  and  consider  a  metastatic  colloid  goiter 
as  a  benign  tumor.  On  the  other  hand,  Kaufmann,  Borst  and  Hanse- 
mann  are  unanimous  in  considering  such  tumors  as  malignant.  In  their 
judgment  the  denomination  of  "benign"  applied  to  a  tumor  which  is 
capable  of  metastasis  is  certainly  in  contradiction  to  what  we  know  of 
benignancy.     Langhans,  too,  considers  this  tumor  as  a  malignant  one. 

It  cannot  be  denied  there  are  cases  in  which  the  metastatic  organ 
was  found  to  be,  histologically,  a  simple  goiter,  which  after  surgical 
removal  never  gave  any  recurrence.  The  only  sign  of  malignancv  was 
its  metastatic  feature.  On  the  other  hand,  metastases  of  benign  tumors, 
as  fibroma,  myoma,  adenoma,  have  been  reported  by  good  authorities. 
For  instance,  Cohnheim  reported  a  case  of  simple  goiter  in  which  he 
was  able  to  find,  microscopically,  epithelial  cords  penetrating  the  walls 
of  a  vein  and  floating  freely  into  the  lumen.  In  such  conditions  metas- 
tasis is  easily  understood.  We  know  that  normal  organs,  as  placenta, 
liver,  and  suprarenal  bodies,  whose  cells  are  in  intimate  relation  with 
bloodvessels,  may  cause  metastases  without  having  shown  anv  sign  of 
malignancy.  Why  should  not  this  be  possibly  the  case  for  the  thvroid 
gland  ?  At  any  rate,  for  some  reason  or  other,  a  few  normal  cells  are 
carried  away  by  the  blood  stream  into  other  organs.  Under  ordinary 
circumstances  these  cells  would  decay,  but  for  some  unknown  reason 
they  find  a  favorable  "terrain"  on  which  they  grow  and  finallv  develop 
to  the  size  of  a  tumor.  This  feature  is  no  longer  to  be  wondered  at  since 
the  illuminating  experiments  of  Carrel,  who  has  been  able  to  grow  in 
cultures  normal  cells  of  different  organs. 

If  we  accept  Ehrhardt's  definition  of  a  malignant  goiter,  "An  intra- 
or  extracapsular  tumor  whose  elements  invade  the  capsule,  encroach 
upon  the  neighboring  tissues  and  cause  metastases,"  we  will  see  that 
in  the  metastatic  colloid  goiter  the  encroaching  upon  the  neighboring 
tissues  and  the  invasion  of  the  capsule  by  the  glandular  elements  are 
absent.      I  he  metastatic  feature  is  the  only  remaining  sign  of  malignancy. 


72  PATHOLOGY 

What  strikes  us  in  the  history  of  a  real  malignant  goiter  is  that 
there  was  at  first  a  simple  goiter  of  more  or  less  long  standing,  that  it 
suddenly  began  to  grow  rapidly,  and  only  later  on  gave  rise  to  metas- 
tases in  the  organs.  This  is  not  the  case  of  the  metastatic  colloid  goiter; 
there  is  here  no  such  history  as  that  of  the  rapid  development  of  a  tumor. 
Regensburger,  in  going  over  the  statistics  of  58  cases,  found  that  the 
time  which  elapsed  between  the  beginning  of  the  metastases  and  the 
death  of  the  patient  was  from  1  to  17  years.  In  all  cases  death  was  not 
due  to  the  goiter,  but  to  an  intercurrent  disease.  Therefore  I  am  forced 
to  admit  that  a  metastatic  colloid  goiter  may  be  in  some  cases  a  benign 
tumor. 

Parastruma  or  Glycogen-containing  Goiter. — Dr.  T.  H.  Kocher,  Jr., 
was  the  first  to  describe  this  form  of  goiter.  It  has  a  nodular  appear- 
ance, grows  rapidly  and  soon  becomes  adherent  to  the  neighboring 
tissues;  it  is  very  hard  in  consistency,  and  rapidly  causes  pressure  symp- 
toms. The  cut  curface  is  gray  or  grayish  white  and  shows  a  typical, 
irregular,  alveolar  structure. 

Its  cells  are  large  and  clear  and  measure  in  diameter  from  20  to  30  /i. 
They  are  polyhedric,  sharply  outlined  with  a  colorless  colloid  body,  and 
have  no  granular  protoplasm  staining  with  eosin.  Such  cells  contain  gly- 
cogen in  variable  quantity,  detected  by  specific  stainings.  Nuclei  are 
round  and  vesicular. 

Smaller  granulated  cells,  staining  with  eosin,  not  so  sharply  out- 
lined as  those  previously  described,  and  not  containing  glycogen,  are 
usually  distributed  all  over  the  tumor  and  mixed  with  cells  containing 
glycogen. 

The  alveoli  are  separated  by  septa  formed  by  capillaries  which 
have  the  same  lacunar  aspect  as  the  ones  spoken  about  in  the  prolifer- 
ating goiter.  In  between  the  alveoli  glandular  canals  lined  with  cylin- 
drical cells  disposed  in  two  or  more  layers  are  found.  Their  nuclei, 
instead  of  being  at  the  base,  lie  at  the  tip  end  of  the  cell  near  the  alve- 
olar lumen.  They  are  of  embryonic  origin  and  correspond  to  the  ves- 
icles and  canals  which  Kiirsteiner  found  extending  from  the  lower  por- 
tion of  the  parathyroid  bodies  to  the  upper  part  of  the  thymus  gland. 
They  have  about  the  same  dimensions  as  the  tubuh  contorti  of  the  kid- 
ney, and  possess  a  high,  clear,  cylindrical  epithelium  with  a  nucleus 
lying  at  the  upper  tip  end  of  the  cell.  Such  canals  may  be  found  even  in 
the  thymus  itself;  they  disappear  at  birth. 

On  the  other  hand,  Getzowa  discovered  in  normal  thyroids  residues 
of  aberrant  parathyroids  containing  glycogen  and  glandular  cells, 
resembling  entirely  those  above  described.  We  know  that  the  human 
parathyroids  usually  contain  glycogen;  that  they  contain  sometimes 
glandular  canals   lined  with  a  high,  clear,  cylindrical  epithelium  whose 


PLATE    III 


Struma  Postbranchialis. 

Nodule  A  sharply  outlined  from  the  rest  of  the  gland.  Note  how  staining  A  differs 
from  staining  of  thyroid  epithelium  B.  A  forms  a  cellular  mass  suggesting  alveoli 
formations  in  places.      X  62. 


FIG.   2 


m 


Cancroid. 
Typical  cancerous    pearls.     X  70. 


MALIGNANT  GOITERS  73 

nuclei  lie  at  the  upper  pole  of  the  cell.  Therefore  it  seems  safe  to  con- 
clude that  a  tumor  containing  glycogen  and  whose  cylindrical  cells  have 
a  nuclei  at  the  tip  end  of  the  cell  instead  of  at  the  base,  is  derived  from 
the  parathyroid  bodies;  hence  the  name  parastruma. 

Parastruma  gives  metastases  in  the  cervical,  mediastinal,  bronchial 
glands,  lungs,  and  bones.  Metastases  may  or  may  not  contain  glyco- 
gen but  possess  the  same  characteristic  cells;  they  contain,  too,  a  great 
quantity  of  mucine  not  found  in  the  parathyroid  bodies. 

Postbranchial  Goiter. — Macroscopically,  this  tumor  is  composed  of 
large  nodules  of  more  or  less  irregular  surface,  sharply  outlined  from  the 
rest  of  the  gland.  The  cut  surface  is  alveolar,  shows  fine  granulations 
and  is  of  a  grayish-brown  or  grayish-red  color.  This  tumor  grows  very 
rapidly. 


*» 


»  »w  I,'  •  4 


Fig.  17. — Struma  postbranchialis.  Large  cells  resembling  liver  cells.  Note  large 
homogeneous  body  of  protoplasm  with  round,  vesicular  nuclei  containing  small  corpuscles 
of  chromatin  and  in  places  an  eccentric  nucleole.      X  700. 

The  alveoli  are  very  small  and  seldom  have  a  diameter  of  more  than 
100  ft.  The  cells  measure  from  1  5  to  30  n,  and  show  a  large  homogeneous, 
refringent  protoplasm.  They  are  polyhedric;  their  nuclei  have  about 
the  same  size  as  the  nuclei  of  normal  thyroid  glands;  they  are  round, 
vesicular  and  contain  small  corpuscles  of  chromatin;  a  small  eccentric 
nucleole  is  almost  always  present.  Such  cells  stain  intensely  with  acids 
and  do  not  contain  fat  or  glycogen. 

They  resemble  greatly  the  cells  of  the  liver  or  suprarenal  bodies. 
T  heir  vesicular  arrangement  and  their  colloid  content  show  their  true 
origin,  and  prevent  mistaking  them  for  the  liver's  or  the  chromaffin 
system's  epithelium. 


74 


PATHOLOGY 


Metastases  are  found  in  the  lungs,  liver,  in  the  lymphatic  glands  of 
the  neck  and  of  the  mediastinal  space,  and  occur  through  the  lymphatic 
vessels. 

Getzowa  has  found  in  normal  thyroid  glands  groups  of  cells  having 
exactly  the  same  histological  appearance  as  the  cells  described.  They 
are  polyhedric,  with  an  abundant  granulated  protoplasm,  staining 
intensely  with  eosin.  (Plate  III,  Fig.  I.)  The  cells  are  sharply  outlined 
and  resemble  the  liver  cells  (Fig.  17).  They  form  solid  cellular  groups, 
and  in  places  beautifully  formed  vesiculi  in  which  there  is  found  col- 
loid. They  are  embryonic  residues 
of  the  postbranchial  bodies,  hence  the 
name  postbranchial  goiter. 

Papilloma. — Papilloma  are  usually 
small  in  size,  and  may  have  a  diffuse 
or  nodular  form.  The  nodules  are 
small,  smooth  in  surface,  with  a  firm, 
fleshy  consistency.  The  cut  surface 
is  finely  granulated,  grayish  red,  and 
may  show  a  lobular  structure.  The 
tumors  may  be  solid  or  cystic.  In 
the  cystic  form  the  most  striking 
and  arborescent  papillary  formations 
may  be  seen  sprouting  from  the  walls 
of  the  tumor  into  the  interior  of  the 
cyst  (Fig.  18). 

Papilloma  begins  to  develop  in 
a  small  follicle  lined  with  one  layer 
of  epithelium;  this  is  the  first  indi- 
cation   of  a    papilla.      It   gradually 
grows  larger,  and   in    a    later    stage 
subdivides     into     smaller    branches 
which    subdivide    themselves  again, 
giving,  finally,  rise  to  the  most  com- 
plicated arborization  (Fig.  19).     In 
places  the  branches  of  the  arborization  meet  together  and  form  vesicles 
in  which  colloid   may  be  found  (Fig.  20).     Capillary  vessels  penetrate 
only  later  in  the  axis  of  the  papillae  and  of  its  arborization. 

The  cells  are  generally  large  and  provided  with  abundant  proto- 
plasm which  is  granular,  not  refringent,  and  stains  readily  with  eosin. 
Cuboidal  or  cylindrical,  they  may  be  sometimes  very  high  and  may 
reach  40,11.  The  nuclei  are  round  or  oval,  lying  at  the  base  of  the  cell 
or  at  its  tip.     They  contain  a  nucleole  staining  with  eosin. 

This   tumor  makes   metastases   especially   in   the   lymphatic  glands, 


Fig.  18. — Papilloma  partly  cystic  and 
partly  solid.  In  the  solid  portion  the 
papillae  fill  up  entirely  the  whole  space. 
In  the  cystic  portion  exquisite  arboriza- 
tions are  seen. 


MALIGNANT  GOITERS 


75 


and   has   a   great   tendency   to   encroach  upon  the  neighboring   tissues. 
Metastases  have  the  same  histological  picture  as  the  primary  tumor. 


Fig.   19. — Papilloma.     This  low  power  shows  plainly  the  arborescent  formations.      X  17. 

JSBSEem  MPISr^  ,* 


oi  a 


t\ 


.*'  -••  •' 


Fig.  20. — Papilloma.     Low  cylindrical  epithelium  and  alveoli  formations  containing 

colloid,     x  125. 


'(■) 


PATHOLOGY 


In  such  tumors  lymphoid  masses  may  be  found,  many  of  them  pos- 
sessing a  distinct  germinal  center.  The  fact  that  cells  with  nuclei  at 
the  upper  end  are  found,  shows  that  they  very  likely  take  their  origin 
in  the  Kiirsteiner  canals,  described  in  relation  with  postbranchial  goiter. 

Cancroid. — This  tumor  never  reaches  enormous  dimensions.  It  has 
an  irregular  surface,  is  very  hard  in  consistency,  and  may  occur  in  normal 
thyroid  gland  as  well  as  in  preexisting  goiter.  The  cut  surface  is  white, 
a  marrow-like  color,  and  is  finely  granular;  the  granulations  are  formed 
by  the  cancerous  nest  sticking  out,  and  can  be  readily  expressed. 


^ 


Fig.  21. — Cancroid.     Broad,  solid,  cellular  cords  of  irregular  size  and  form, 
embedded  in  more  or  less  loose  connective  tissue.      X  44. 

Histologically,  this  tumor  gives  the  same  microscopic  picture  as  the 
cancroid  developed  in  the  skin,  mouth,  pharynx,  esophagus,  and  other 
organs  containing  a  cuboidal  epithelium.  It  is  formed  by  broad,  solid 
cords  of  irregular  size  and  form  (Fig.  21)  embedded  in  a  more  or  less 
loose  connective  tissue  and  formed  of  polyhedric  cells  provided  with  an 
abundant  protoplasm.  This  protoplasm  is  finely  granular  and  does  not 
take  eosin  easily.  It  contains  in  its  center  a  very  large  vesicular  nucleus 
which  contains  a  few  small  nuclei  of  chromatin.  (Plate  III,  Fig.  2.) 
Cancer  pearls  are  numerous;  the  blood  supply  is  not  diminished,  and 
stroma  is  generally  highly  developed. 


MALIGNANT  GOITERS  77 

Owing  to  the  fact  that  such  tumors  have  always  a  close  connection 
with  the  pharynx  or  larynx,  Langhans  thinks  that  this  tumor  has  its 
starting-point  in  the  epithelium  of  the  pharynx,  larynx  or  in  remnants 
of  the  thyroglossus  duct.  The  fact  that  this  tumor  always  develops 
and  perforates  at  the  same  place,  namely,  near  and  behind  the  first 
tracheal  ring,  seems  to  support  this  theory.  On  account  of  its  com- 
munication with  the  larynx  or  pharynx  this  tumor  is  oftentimes  the 
seat  of  inflammation  and  has  a  tendency  to  necrosis.  Being  given 
its  anatomical  relations  it  involves  earl}'  the  sympathetic  and  inferior 
laryngeal  nerves.     This  tumor  is  rare. 

Tumors  of  Connective-tissue  Origin. — Sarcoma  of  the  thyroid  gland 
occurs  sometimes  in  earl)'  life,  but  in  the  greatest  majority  of  cases  it  is 
to  be  found  between  fifty  and  sixty  years.  Molf  thinks  that  he  found  a 
suitable  explanation  for  this  in  the  fact  that  in  advanced  age  epithelial 
elements  undergo  atrophy,  thus  allowing  the  connective  tissue  to  grow 
with  energy. 

Sarcoma  develops  with  preference  in  nodular  goiter,  where  the  con- 
nective tissue  may  be  found  more  or  less  abnormally  developed  and 
undergoing  degenerative  and  metaplastic  changes.  It  may  reach  larger 
dimensions,  being  formed  by  a  mass  of  conglomerated  nodules,  more 
or  less  large  in  size. 

Sarcoma  grows  extremely  rapidly.  In  the  early  stage  it  is  mobile 
and  sharply  limited,  but  later  it  becomes  adherent  to  the  neighboring 
tissues,  muscles,  trachea,  esophagus,  etc.  Hence  the  diffuse  limits,  loss 
of  mobility,  difficulty  in  swallowing,  irradiating  pain  in  the  ear,  in  the 
arm,  etc.  The  common  carotid  is  displaced  backward;  exceptionally,  it 
may  be  completely  surrounded  by  the  tumor.  Sarcoma  is  soft  in  consist- 
ency, friable,  exudes  little  juice  or  none  on  its  cut  surface,  which  is 
grayish  white  in  color.  Its  blood  supply  is  generally  increased.  It  has 
a  great  tendency  to  undergo  necrosis,  fatty  degeneration,  or  calcification. 

The  varieties  of  sarcoma  mostly  found  in  the  thyroid  gland  are: 

1.  Fibrosarcoma. 

2.  Polymorphous-cell  sarcoma. 

3.  Round-cell  sarcoma. 

4.  Myxosarcoma. 

5.  Endothelioma. 

6.  Perithelioma. 

1.  Fibrosarcoma. — This  variety  is  the  most  frequent.  It  is  gener- 
ally of  harder  consistency  than  the  round-cell  sarcoma,  but  it  may  be 
soft  also.  Its  outer  surface  is  lobulated  and  its  cut  surface  is  grayish 
white  or  yellowish  white,  but  it  may  be  of  a  brownish-red  color  it  the 
blood  supply  is  very  well  developed.  This  form  of  sarcoma  is  less  malig- 
nant  than   the   round-cell   sarcoma.      Histologically,   it    does   not   differ 


78 


PATHOLOGY 


from  the  picture  of  fibrosarcoma  in  general;  the  cells  form  a  long  spindle 
in  which  nuclei  are  found.  Spindle  cells  alternate  with  masses  of  gen- 
uine connective  tissue;  hence  the  name  fibrosarcoma. 

2.  Polymorphous-cell  Sarcoma. — This  sarcoma  is  a  mixture  of  spindle, 
round,  and  pyramidal  cells.  Giant  cells  may  be  present  also.  In  fre- 
quency this  form  of  tumor  comes  next  to  the  spindle-cell  sarcoma. 

3.  Round-cell  Sarcoma. — The  round-cell  sarcoma  forms  a  soft,  rap- 
idly growing  tumor.  As  it  is  generally  composed  of  several  lobes  its 
outer  surface  is  lobulated.  The  cut  surface  is  generally  white  and  con- 
tains necrotic  areas.  A  white,  milky  juice  exudes.  The  blood  supply 
of  the  round-cell  sarcoma  is  generally  intensely  developed.     The  cells 


Fig.  22. — Round-cell  sarcoma.     The  small,  round  sarcomatous  cells  are  seen  penetrating 
between  the  alveoli;  many  of  them  are  already  about  destroyed.      X  50. 


of  this  form  of  sarcoma  penetrate  between  the  follicles  of  the  thyroid 
gland  and  surround  and  destroy  them  entirely  (Fig.  22),  so  that  the 
microscopic  examination  of  a  well-developed  tumor  shows  only  round- 
cell  sarcoma.  No  trace  of  a  follicle  is  found  except  at  the  periphery  of 
the  tumor,  where  the  folliculi  have  not  been  entirely  destroyed. 

The  round-cell  sarcoma  has  two  kinds  of  cells:  the  small  and  the 
large.  The  small  cells  are  composed  of  a  nucleus  with  a  thin  layer 
of  protoplasm.  They  resemble  lymphoid-tissue  cells  very  much.  The 
variety  with  large  round  cells  contains  abundant  and  granular  proto- 
plasm. The  nucleus  is  large  and  oval.  The  latter  variety  is  less  malig- 
nant than  the  sarcoma  with  small  round  cells. 


PLATE    IV 


** 


Endothelioma. 

Endothelial  cells  of  a  vascular  lacuna.     Note  enormous  dimensions  acquired  by  the 
endothelium  a;  blood,  b.     X  280. 


MA  LIGXA  N  T  GDI TERS 


!9 


4.  Myxosarcoma. — Myxosarcoma  is  a  rare  tumor  and  does  not  differ 
materially  from  fusocellular  sarcoma.  It  is  formed  by  fusiform  sarco- 
matous cells  and  abundant  mucinoid  tissue. 

5.  Endothelioma. — Macroscopically,  the  endothelioma  is  sharply  out- 
lined; only  later  when  the  capsule  and  neighboring  tissues  have  been 
invaded  by  the  tumor  does  it  become  diffuse  in  its  limits.  The  surface 
is  more  or  less  coarsely  lobulated  because  the  tumor  may  be  composed 
of  one  or  more  nodules  of  different  sizes.  Its  capsule,  more  or  less  thick, 
is  composed  of  connective  tissue  in  which  bloodvessels  have  been  partly 
obliterated;  hence  the  frequent  areas  of  necrosis  found  throughout  the 
tumor.  The  cut  surface  differs  strikingly  from  the  cut  surface  of  other 
varieties  of  sarcoma.  Connective  tissue  irregularly  disposed  forms,  a 
framework  in  which  large  vascular  lacunes   are  found  containing  liquid 


Fig.  23. — Endothelioma.     Cavernous  portions  of  the  tumor.      X  60. 

or  coagulated  blood  (Fig.  23).  Fibrin  at  different  stages  of  organization 
is  seen  forming  gray  masses  which  have  been  called  by  Langhans 
"rubber  colloid." 

The  microscopic  picture  seems  to  be  at  first  very  complicated.  This 
tumor  is  composed  of  capillary  vessels  with  a  single  layer  of  epithelium; 
little  by  little  the  epithelium  begins  to  proliferate;  the  capillary  vessels 
become  larger  and  finally  form  large  (Plate  IV)  vascular  lacunes  filled 
with  blood  in  which  the  epithelium  has  acquired  enormous  dimensions. 
I  his  endothelium  may  be  desquamated,  and  in  places  fills  entirely  the 
vascular  cleft,  thus  forming  solid  cellular  cords  and  nests. 

In  places  large  endothelial  cells  are  found  containing  in  their 
protoplasm  one  or  several  red  corpuscles  undergoing  degeneration  and 
finally  forming  homogeneous  little  lumps  known  as  Russell's  corpuscles. 
This  shows  the  exquisite  phagocytic  power  of  endotheliomata. 


SO  PATHOLOGY 

The  cells  are  variable  in  form.  They  may  be  polyhednc,  round,  or 
have  a  spindle  form;  protoplasm  is  more  or  less  abundant  and  stained 
heavily  with  eosin.  The  nuclei  are  generally  large  and  contain  one  or 
two  small  corpuscles  of  chromatin. 

Connective  formations  between  the  vascular  lacunes  are  more  or 
less  abundant.  Metastases  take  place  through  the  bloodvessels  and 
have  the  same  characteristics  as  the  primary  tumor. 

6.  Perithelioma. — Such  tumors  originate  by  proliferation  of  the 
outermost  part  of  the  wall  of  the  bloodvessel.  The  endothelium  is 
always  normal,  its  outermost  part  only  showing  the  beginning  of  the 
proliferation. 

The  microscopic  picture  is  very  typical.  It  consists  of  a  capillary 
vessel  of  more  or  less  large  diameter  with  an  absolutely  normal  endothe- 
lium. All  around  this  lumen  there  are  multiple  layers  of  cells  forming 
a  thick  mantle  to  the  bloodvessels.  These  mantles  may  be  separated 
or  may  fuse  together,  forming  what  is  called  a  plexiform  angiosarcoma. 
When  fusion  between  the  mantles  has  not  taken  place,  capillary  vessels 
and  thyroid  follicles  may  be  found. 

The  cells  may  be  more  or  less  large  and  of  different  forms.  The 
protoplasm  stains  readily  with  eosin,  and  its  nucleus  contains  many 
small  nucleoles  of  chromatin.     Such  tumors  are  generally  very  hard. 

Combination  of  Various  Forms  of  Malignant  Goiter. — Carcinoma  and 
sarcoma  may  occur  at  the  same  time  in  the  thyroid  gland.  This  occur- 
rence, however,  is  exceedingly  rare.  Such  tumors  are  formed  with 
cells  of  the  carcinomatous  and  sarcomatous  type  irregularly  mixed 
together;  hence  the  name  carcinoma  sarcomatodes.  Schmorl  has  seen 
carcinomata  sarcomatodes  occur  in  a  relapsing  cancer  of  the  thyroid 
gland.     In  the  metastasis  the  sarcomatous  type  of  cells  only  was  found. 

Mixed  Tumors. — These  tumors  are  characterized  by  their  extreme 
polymorphic  aspect,  as  they  contain  connective  and  epithelial  tissues, 
cartilage,  bone,  etc.  They  have  been  called  osteochondrosarcoma  and 
osteochondroadenoma,  etc.  They  constitute  the  first  stage  in  the  develop- 
ment of  teratoma,  with  the  difference  that  they  do  not  contain  any 
well-differentiated  organ  like  the  latter  one. 

These  tumors,  although  found  mostly  in  old  people,  seem  to  be  con- 
genital. They  undergo  malignant  degeneration  only  in  old  age.  Women 
have  them  more  often  than  men,  and  they  are  found,  too,  in  animals. 
Their  size  varies  from  the  size  of  a  fist  up  to  the  size  of  the  head  of  a 
fetus.  Their  surface  may  be  smooth,  but  is  mostly  grossly  lobulated. 
They  are  firm  or  hard  in  consistency,  although  some  portions  may  be 
soft.  As  a  rule  the  tumor  has  sharp  limits  except  in  advanced  stages  of 
malignancy.  Their  walls  are  often  infiltrated  with  calcareous  deposits, 
so  that  a  saw  is  necessary  to  cut  them.      In  the  cut  surface   the    carti- 


MALIGNANT  GOITERS  81 

laginous  and  bony  formations  are  found  mixed  with  softer  areas  formed 
by  sarcomatous  or  cancerous  degeneration.  These  tumors  produce 
metastases  in  the  lungs,  heart,  suprarenal  bodies,  liver,  stomach,  and 
intestines.  The  lungs  are  mostly  affected.  The  histological  picture  of 
the  metastasis  is  the  same  as  that  of  the  original  tumor;  bone,  cartilage 
and  other  tissues  may  be  found  in  it. 

Histologically,  osseous  and  cartilaginous  tissues  are  found  diffusely 
mixed  with  thyroid  elements;  the  alveoli  may  proliferate  intensely  and 
their  epithelium  in  places  may  become  cylindrical.  Colloid  is  also 
present  in  alveoli. 

The  most  common  form  of  degeneration  of  connective  tissue  is  the 
fusocellular  sarcomatous  type.  Blood  is  supplied  bv  vascular  lacunes 
whose  thin  walls  will  explain  easily  why  hemorrhages  are  frequent  in 
such  tumors. 

Hyalin  and  reticular  cartilage  are  more  or  less  constantly  found  in 
mixed  tumors  of  the  thyroid.  Their  distribution  throughout  the  tumor 
is  capricious  and  does  not  follow  any  rule.  The  osseous  elements  have 
not,  like  normal  bones,  a  lamellous  structure;  the  osseous  corpuscles  are 
not  as  well  formed  as  the  normal  ones.  As  a  rule  the  structure  of  these 
bony  formations  affects  the  spongiform  type;  the  eburneous  type  is  rare. 
No  medulla  is  found  in  the  trabecules. 

Solarno,  of  Milan,  reported,  in  1914,  a  case  of  osteosarcoma  devel- 
oped in  the  left  lobe  of  the  thyroid.  The  tumor  was  enucleated  but 
recurred  quite  rapidly.  It  was  formed,  histologically,  of  sarcomatous  and 
osteoid  elements. 

The  pathogen}'  of  such  tumors  can  be  explained  by  the  theory  of 
metaplasia;  in  other  words,  they  are  due  to  an  abnormal  and  incoherent 
proliferation  of  normal  glandular  elements.  Such  conception  is  based 
on  indisputable  facts  of  substitution  of  one  tissue  by  another;  for 
instance,  the  ossification  of  a  scar  tissue  in  the  abdominal  wall  after  a 
laparotomy  is  a  well-known  fact.  While  assistant  to  Professor  Kocher 
I  remember  that  eight  to  ten  months  after  a  median  laparotomy  for  a 
gastric  cancer  we  removed  a  large  ossification  which  had  developed  in 
the  old  scar;  histologically,  it  proved  to  be  ossified  connective  tissue. 

Cohnheim  explains  the  origin  of  such  tumors  by  the  inclusion  theory. 
In  his  judgment  some  non-differentiated  cellular  elements  of  other 
organs  are  accidentally  mixed  and  held  among  the  thyroid  cells  at  the 
time  of  their  embryological  formation.  For  a  long  time  they  remain 
inactive,  but  in  later  periods  of  life,  for  some  unknown  reason,  they 
begin  to  proliferate  and  develop  into  these  peculiar  tumors. 

Dermoids  and  Teratoma.  -These  tumors  ait-  exceedingly  rare;  three 
or  four  cases  have  been   reported   in    the   literature.       I  hey    represent    ;i 
step  further  in  the  development  of  mixed  tumors.      In   the  latter  ones 
6 


82  PATHOLOGY 

the  elements  are  mixed  together  without  order  and  are  represented  by 
a  cellular,  non-differentiated  mass;  whereas  in  dermoids  and  teratoma, 
these  elements  are  organized  into  rudimentary  organs  as  skin,  hair  and 
other  well-developed  tissues. 

Personally,  I  came  across  one  case  (Fig.  24).  The  dermoid  in  itself 
was  a  very  small  nodule  about  the  size  of  a  small  nut,  mixed  among 
other  colloid  nodules.  There  was  no  infiltration 
of  the  neighboring  tissues,  and  the  only  feature 
which  attracted  my  attention  was  its  white, 
transparent  appearance.  Microscopically,  it 
proved  to  be  skin  with  sebaceous  and  sudori- 
parous glands.     (Plate  V,  Figs.  1  and  2.) 

Accessory  Goiters. — An  accessory  goiter  is  a 
goiter  developed   in    an  accessory  thyroid   gland. 

r  t\         .1  We   distinguish    two    kinds   of  accessory    goiters, 

tig.  24. — Dermoid  cyst.  &  .  . 

Natural  size.  tne   fa^se  ar>d    the   genuine.     If  a  goiter   nodule 

gradually  becomes  separated  from  the  main  body 
of  the  thyroid,  so  as  to  be  wandering,  possibly  quite  far  from  the 
mother-land,  while  retaining  with  it  a  connective-tissue  connection, 
this  wandering  goiter  is  called  false  accessory  goiter;  but  if  the  accessory 
goiter  nodule  has  no  connection  whatsoever  with  the  thyroid  or  the 
goiter,  then  it  is  called  genuine  accessory  goiter. 

Genuine  accessory  goiter  takes  its  origin  in  residues  left  at  the  time 
of  the  formation  of  the  thyroid.  We  must  remember  that  after  the 
thyroglossus  duct  has  proliferated  and  formed  the  thyroid  gland,  it 
gradually  becomes  atrophied  and  leaves  as  vestiges  a  fibrous  cord  called 
the  thyroglossus  tract,  which  extends  from  the  foramen  cecum  of  the 
tongue  to  the  pyramidal  process  of  the  thyroid,  passing  between  the 
mylohyoid  and  the  geniohyoid  muscles.  This  duct  may  leave  along  its 
entire  course  islands  of  thyroid  tissue,  at  the  cost  of  which  later  on 
accessory  glands  or  goiters  may  develop.  Sometimes  the  thyroglossus 
tract  passes  behind  or  in  front,  or  even  through  the  hyoid  bone,  and 
may  extend  downward  into  the  anterior  mediastinal  space  as  far  as  the 
aorta.  In  that  case  accessory  glands  may  be  left  over  the  entire  length 
of  this  course  and  thus  will  be  easily  explained  the  origin  of  accessory 
glands  and  of  tumors  of  the  mesobranchial  type,  developed  not  only  at 
the  base  of  the  tongue,  in  the  hyoid  bone,  and  in  the  cervical  region, 
but  also  in  the  mediastinal  space. 

Accessory  goiters  may  be  influenced  sympathetically  by  pathological 
disturbances  of  the  thyroid  gland  itself;  they  may  undergo  compensa- 
tory hypertrophy  after  partial  or  complete  thyroidectomy;  finally,  they 
may  give  rise  to  the  same  variety  of  tumors  as  the  gland  itself.  Conse- 
quently, whenever  the  presence  of  an  accessory  goiter  is  suspected,  the 


PLATE    V 


M 


\ •  VJ*    VH*  few  %»«&< 


c< 


Dermoid  of  Thyroid. 
Skin  with  (a)  stratum  corneum;  &,  stratum  mucosum;  c,   stratum   conjunctivum. 

X  3°°- 


FIG.   2 


Dermoid  of  Thyroid. 
a,   sebaceous  glands;  b,   stratum   pilosum.      X  ioo. 


MEDIAN  CYSTS     '  83 

th)rroid  gland  should  be  thoroughly  examined,  as  the  treatment  will 
depend  greatly  upon  the  conditions  found.  If  the  thyroid  is  function- 
ally' intact,  excision  of  the  accessory  goiter  can  be  done  safely;  but  if 
symptoms  of  thyroid  insufficiency  are  present,  a  partial  operation  onlv 
on  the  accessory  goiter  must  be  performed. 

The  most  important  varieties  of  accessor)'  goiters  are  the  median 
cysts  and  lingual  goiters;  then  come  the  intrathoracic,  the  intratracheal, 
and  ovarian  goiters. 

Median  Cysts. — Median  cysts  are  located  above  or  under  the  hvoid 
bone;  more  rarely  they  are  located  in  the  body  of  the  hvoid  bone  itself. 
Although  variable  in  volume,  they  seldom  exceed  the  size  of  an  egg. 
Thev  are  round  or  oval  in  shape,  elastic  in  consistency,  often  show 
fluctuation,  being,  as  a  rule,  firmly  attached  to  the  hvoid  bone;  they 
are  more  or  less  immobile;  pressure  is  painless.  They  originate  from  an 
incompletely  obliterated  thyroglossus  duct  (Fig.  25),  giving  off  a  secre- 
tion which  gradually  distends  the  canal  until  a  cyst  is  formed.  They 
are  seldom  congenital.  As  a  rule  they  develop  in  the  first  three  decades 
of  life  and  are  more  frequently'  observed  at  the  time  of  puberty. 

The  following  case  will  serve  as  a  good  illustration  of  such  a  condition: 

Miss  H.  C,  aged  twenty  years,  referred  to  me  by  Dr.  J.  F.  Baldwin, 
of  Columbus,  Ohio.  A  year  before  the  patient  noticed  a  small  lump 
under  the  chin,  growing  slowly  but  gradually;  no  pain;  no  disturbance 
of  any  kind.  Examination  showed  that  between  the  hvoid  bone  and 
the  thyroid  cartilage,  in  front  of  the  thyrohyoid  membrane,  there  was 
a  lump  the  size  of  a  walnut,  with  smooth  surface,  elastic,  and  slightly 
mobile  laterally,  but  immobile  in  the  upward  direction;  pressure  was 
absolutely  painless.  Thyroid  gland  was  normal  and  independent  of  the 
tumor. 

Diagnosis. — Cyst  of  the  thyroglossus  duct. 

Operation  confirmed  the  clinical  diagnosis  and  showed  a  cyst  dark 
in  color,  situated  between  the  hvoid  bone  and  the  thyroid  cartilage  in 
front  of  the  thyrohyoid  membrane.  The  thyroid  cartilage  was  dis- 
placed downward,  forming  a  part  of  the  lodge  in  which  the  cyst  was 
located.  The  cyst  was  attached  firmly  to  the  hvoid  bone  and  was 
solidly  embedded  in  it.  It  was  carefully  dissected  out  and  removed. 
The  walls  of  the  cyst  were  thin  and  contained  a  dark  tluul  rich  in  choles- 
terin.  At  the  microscopic  examination  the  walls  of  the  cyst  were  found 
to  be  lined  with  a  ciliated,  cylindrical  epithelium  disposed  m  one,  two, 
and,  in  places,  three  layers. 

The  epithelium  lining  these  cysts  is  not  always  cylindrical,  bur  may 
be  pavimentous.  The  cystic  contents  may  be  a  clear  or  bloody  fluid 
containing  cholesterin. 

The  median  fistula  may  be  complete  or  incomplete.     In   rlu-  great 


84 


PATHOLOGY 


majority  of  cases  it  is  not  congenital,  but  appears  after  birth.     If  com- 
plete, the  fistula  extends  from  the  foramen  cecum  of  the  tongue  to  the  skin, 


FlG  25._Diagram  showing  the  various  locations  of  cystic  or  solid  tumors  developed 
from  the  thyroglossus  duct,  i,  intralingual;  2,  sublingual;  3,  suprahyoid;  4,  infrahyoid; 
5,  prethyroid. 

its  external  orifice  being  found  on  the  middle  line  of  the  neck  between  the 
hyoid  bone  and  the  jugulum.     Its  external  opening  may  be  punctiform  or 


LINGUAL  GOITER  85 

may  be  wider.  Its  lumen  may  be  unique  or  multiple.  Oftentimes  the 
walls  of  the  fistula  are  so  thickened  as  to  become  easily  palpable  under 
the  skin,  especially  in  the  region  of  the  hyoid  bone.  It  passes  in  front 
of  the  incisura  of  the  thyroid  cartilage  and  in  front  of  the  thyrohyoid 
ligament  and  forms  intimate  relations  with  the  hyoid  bone,  while  passing 
behind,  in  front,  or  through  the  bod}'  of  that  bone.  The  epithelium 
lining  the  canal  may  be  cylindrical  or  pavimentous  or  both  together; 
secretion  is  variable  and  may  be  reduced  to  a  few  drops  a  day  or  mar  be 
quite  abundant;  in  that  case  irritations  and  eczematous  conditions  of 
the  skin  may  follow.  Fistula  and  cyst  may  in  rare  instances  undergo 
malignant  degeneration.     The  only  rational  treatment  is  their  removal. 

Lingual  Goiter. — Lingual  goiter  is  not  infrequently  found.  Accord- 
ing to  Smyth,  67  cases  have  been  reported  in  the  literature.  Out  of 
this  number  61  were  in  females.  Although  found  at  all  ages  of  life,  they 
seem  to  be  most  frequently  reported  at  the  time  of  pubertv.  For  a 
long  time  they  may  remain  unobserved,  but  when  they  begin  to  grow 
the  symptoms  rapidly  become  marked. 

The  tumor  is  always  found  at  the  root  of  the  tongue  in  the  region  of 
the  foramen  cecum,  and  is  usually  median.  The  size  varies  between 
the  size  of  a  cherry  and  that  of  an  egg.  Its  consistency  is  variable;  it 
may  be  hard,  soft  or  cystic,  according  to  the  pathological  changes  which 
have  taken  place  in  it.  Although  embedded  in  the  muscular  fibers  of 
the  tongue,  it  may  have  a  slight  mobility  per  se,  and  has  always,  except 
when  inflamed  or  degenerated,  very  sharp  limits.  Under  the  chin  a 
diffuse  swelling  may  be  seen,  but  toward  the  pharynx  and  larynx  the 
tumor  is  well  outlined. 

Lingual  goiters  are  exceedingly  vascular.  Large,  numerous  blood- 
vessels penetrate  the  goiter  from  the  neighboring  tissues.  The  mucous 
membrane  of  the  tongue  is  congested  and  filled  with  dilated  blood- 
vessels; consequently  a  slight  traumatism  may  cause  quite  an  impor- 
tant hemorrhage;  as  a  result  the  operation  will  be  a  bloody  one. 
Histologically,  these  tumors  are  the  same  as  simple  goiter. 

The  symptomatology  of  such  tumors  has  very  few  characteristics 
of  its  own.  Patients  complain  of  a  sensation  of  fulness  and  tension  in 
the  upper  part  of  the  neck  as  if  a  foreign  body  were  localized  in  the 
pharynx  and  could  not  be  swallowed  despite  continued  efforts  at  degluti- 
tion. If  the  tumor  is  superficially  localized,  the  epiglottis  being  con- 
stantly irritated,  coughing  spells  may  ensue.  Deglutition  and  respira- 
tion are,  as  a  rule,  interfered  with  only  when  the  goiter  h;is  reached  hum 
dimensions.  There  is  often  a  certain  difficult)  of  speech:  the  patient 
articulates  as  if  the  tongue  were  infiltrated  and  swollen.  At  the  same 
time  the  flow  of  saliva  may  be  increased;  expectorations  oi  blood  due 
to  ulcerations  of  the  lingual  mucous  membrane  may  occur. 


86  PATHOLOGY 

Diagnosis  is  not  always  easy.  In  discussing  the  differential  diag- 
nosis of  lingual  tumors  the  possibility  of  a  lingual  goiter  should  always 
be  borne  in  mind.  The  mere  inspection  of  the  buccal  cavity  with  a 
frontal  mirror  is  not  sufficient,  as  in  many  of  the  reported  cases  the 
tumor  could  not  be  seen  by  direct  inspection.  But  indirect  examination 
with  the  laryngoscopic  mirror  will  show  in  the  region  of  the  foramen 
cecum  a  tumor  bulging  more  or  less  and  covered  with  a  congested  and 
vascular  mucous  membrane.  Intrabuccal,  monodigital  examination 
combined  with  outside  manipulation  will  readily  discover  the  tumor; 
as  palpation  is  painless,  its  limits  will  be  easily  outlined.  The  tumor 
may  bulge  slightly  under  the  chin.  Lymphatic  glands  of  the  cervical 
region  are  not  involved. 

In  a  syphilitic  gumma  the  limits  are  more  diffuse  and  the  tumor  has 
a  tendency  to  show  a  softening  of  its  central  portions.  In  malignant 
tumors  the  limits  will  be  infiltrated  and  diffuse.  The  age  of  the  patient 
and  the  course  of  the  disease  may  be  of  some  help  in  differentiating 
the  diagnosis.  Dermoids  and  cystic  tumors  of  branchial  and  salivary 
origin  sometimes  found  at  the  basis  of  the  tongue  may  not  be  differen- 
tiated, clinically,  from  a  lingual  goiter,  as  their  consistency  and  other 
anatomical  features  may  recall  those  of  a  lingual  goiter  to  such  a 
degree  that  their  true  nature  is  recognized  only  at  the  time  of  the  opera- 
tion. Angiomas  are  more  spongy,  more  irregular  in  outline,  of  purple 
color,  and  show  usually  venous  extension  to  one  of  the  lateral  sides  of 
the  pharynx. 

Surgery  is  the  only  rational  treatment  for  such  conditions.  Before 
removing  radically,  care  should  be  taken  to  ascertain  the  presence  of 
some  other  source  of  thyroid  secretion,  as  cases  of  myxedema  have 
been  reported  from  various  sources  as  a  consequence  of  a  radical  extir- 
pation of  a  lingual  goiter.  The  operation  can  be  made  from  within  or 
without  the  mouth.  The  choice  of  the  route  will  be  dictated  by  the 
case  itself.  If  the  buccal  route  is  chosen,  and  if  general  anesthesia  is 
not  used,  the  tongue  and  pharynx  are  carefully  novocainized,  and  a 
rapid  enucleation  is  made  while  the  tongue  is  held  in  extreme  tension. 
The  free  hemorrhage  is  controlled  by  deep  sutures.  If  the  cervical 
route  is  chosen,  a  transverse  incision  is  made  in  the  region  of  the  hyoid 
bone  and  the  goiter  is  dissected  out.  It  will  rarely  be  necessary  to  divide 
the  lower  jaw.  While  bloody,  these  operations  for  lingual  goiter  are 
quite  successful.     No  fatalities  have  been  reported. 

Intrathoracic  Accessory  Goiter. — Accessory  thyroid  glands  are  not 
infrequently  found  in  the  thorax.  Wolfler  called  attention  to  this,  and 
Wagner  found  quite  frequently  small  accessory  goiters  in  the  thoracic 
cavity  of  dogs.  I  remember  finding  at  an  autopsy  of  a  patient  a  tumor 
the  size  of  a  small  egg  situated  at  the  bifurcation  of  the  trachea.  His- 
tologically, this  tumor  was  a  simple  colloid  goiter. 


OVARIAN  GOITER  s7 

These  tumors  have  been  found  in  close  relation  with  the  aorta,  and 
therefore  have  been  called  aortic  goiter. 

While  assistant  to  Professor  Kocher  I  remember  seeing  an  aber- 
rant intrathoracic  goiter  which  during  coughing  spells  became  entirely 
cervical  and  disappeared  again  into  the  chest. 

The  majority,  however,  of  these  tumors  are  autopsy  findings.  Few 
may  grow  so  large  that  marked  symptoms  of  dyspnea  and  impairment 
of  circulation  follow.  The  symptomatology  of  such  tumors  does  not 
differ  from  the  symptomatology  of  intrathoracic  goiter,  which  will  be 
discussed  in  a  later  chapter. 

Ovarian  Goiter. — Ovarian  tumors  showing  both  grosslv  and  histologi- 
cally the  typical  structure  of  a  struma  colloides  have  been  reported  by 
numerous  authors  more  than  once.  A  great  many  of  such  tumors  are 
teratomata  in  which  the  thyroid  tissue  has  taken  the  upper  hand,  but 
in  others  no  teratoid  formations  can  be  found,  so  that  the  tumor  seems 
to  be  composed  purely  of  thyroid  alveoli  with  their  typical  normal 
structure. 

Possibly  such  tumors  are  due  to  metastatic  colloid  goiters.  \\  e 
know  that  a  simple  colloid  goiter  is  liable  to  make  metastases  in  bones 
and  other  organs.  Why  not,  then,  in  the  opinion  of  some  authors, 
admit  that  such  metastases  could  take  place  in  the  ovary:  Thus  the 
question  is  proposed,  but  I  would  not  dare  to  answer  it.  I  should  rather 
be  inclined  to  consider  the  above  theory  as  improbable. 

Similar  tumors  have  been  found  in  the  testicles.  One  should  not 
forget  there  is  a  series  of  tumors  which  might  be  mistaken  for  an  ovarian 
goiter,  and  which  are,  indeed,  tumors  of  an  entirely  different  nature, 
such  as  adenoma,  cystadenoma,  adenocarcinoma,  endothehomata,  etc.; 
in  these,  too,  the  colloid  formation  may  be  very  abundant  and  the 
histological  picture  may  resemble  that  of  goiter. 

Pick  was  the  first  to  contend  that  these  ovarian  goiters  are  all 
teratomata,  whether  they  contain  or  do  not  contain  embryonic  rests 
of  other  organs;  the  thyroid  elements  possessing  more  vitality  out- 
grow the  other  embryonic  tissues  and  finally  destroy  them.  1  his 
process  results  finallv  in  the  production  of  a  colloid  tumor.  In  support 
of  his  contention.  Pick  cites  Saxer's  case,  in  which  a  single  well-formed 
tooth  was  found  in  an  otherwise  healthy  ovary.  In  Pick's  judgment 
this  can  be  explained  only  on  the  theory  that  a  teratomata  had  started 
to  develop,  that  the  tooth  above  was  able  to  grow,  and  that  the 
remainder  of  the  embryonic  tissues  was  absorbed. 

Pick's  views  on  the  etiology  of  ovarian  goiters  are.  so  to  speak, 
universally  accepted.  \\  althard  examined  three  ovarian  goiters  which 
were  apparently  composed  of  thyroid  tissue  only.  x  et,  after  making 
"complete  serial  sections"  of  all  of  these  three  tumors  he  found  in  one 


88  PATHOLOGY 

case  cartilage,  in  the  other  squamous  epithelium,  and  in  the  third  seba- 
ceous and  sweat  glands.  In  every  case  the  findings  were  purely  micro- 
scopic; it  would  have  been  utterly  impossible  to  detect  them  macro- 
scopically.  These  facts  of  Walthard's  very  strongly  support  the  teratoma 
theory. 

The  iodin  content  of  such  tumors  might  be  of  diagnostic  value, 
since  we  know  that  in  goiter,  iodin  more  or  less  is  always  present.  To 
be  pathognomonic  it  should  be  demonstrated  that  iodin  does  not  exist 
in  any  others  except  in  those  of  thyroid  origin.  I  think  that  this  fact 
has  not  been  thoroughly  established.  At  any  rate  the  amount  of  iodin 
found  in  these  thyroid-like  tumors  is  so  infinitesimal  (0.000225  Sm- 
iodin  in  16  gms.  of  ash,  by  Robert  Meyer)  that  its  presence  is  of  com- 
paratively little  significance.  A.  P.  Jones  has  shown  that  the  presence 
or  absence  of  iodin  in  colloid  material  can  be  determined  by  the  behavior 
of  the  colloid  with  the  Mallory's  anilin-blue-orange  connective-tissue 
stain.  G.  W.  Outerbridge,  after  applying  the  same  staining  method  to 
ovarian  goiters,  found  that  these  tumors  contain  without  doubt  a  certain 
amount  of  iodin. 

Such  tumors  may  reach  a  very  large  size  and  are  very  often  accom- 
panied by  ascites;  they  are  coarsely  lobulated,  and  may  be  partly  cystic 
and  partly  solid.  The  only  case  which  it  has  been  my  good  fortune  to 
see,  reminded  me  at  once  on  its  cut  surface  of  a  colloid  goiter;  the  histo- 
logical examination  confirmed  my  presumptions.  Clinically,  most  of 
these  ovarian  goiters  are  benign;  some  of  them,  however,  may  undergo 
malignancy.  Concomitant  ascites  must  be  regarded  as  a  suspicious 
symptom.  Yet  it  is  no  certain  proof  of  malignancy,  since  we  know  that 
ascites  sometimes  accompanies  benign  ovarian  tumors  or  non-malignant 
pediculated  fibroids  of  the  uterus. 

From  all  that  we  know  of  the  physiology  of  the  thyroid  gland,  if 
these  ovarian  goiters  are  truly  of  thyroid  parenchyma,  then  there  can 
be  no  doubt  that  these  tumors  are  endowed  with  an  internal  secretion. 


CHAPTER   V. 


INFLAMMATIONS   OF  THE  THYROID. 


Inflammations. 


I.   Bacterial 

2    Toxic. 
3.   Parasitic. 


Acute 


Non-purulent. 

Purulent. 
Syphilis. 
Chronic.     -  Tuberculosis. 

Ligneous  or  woody  thyroiditis. 


Chagas  thyroiditis. 
Echinococcus. 


History. — As  earl)'  as  the  eighteenth  century  a  number  of  descrip- 
tions of  purulent  and  non-purulent  thyroiditis  were  given  by  Carron, 
Walter,  Hedenus,  Conradi  and  Bischof.  The  disease  was  called  by 
some  "cynanche  thyroidea,"  and  "angina  thyreoidea;"  it  was  called  by 
Walter  "struma  inflammatoria;"  Franck  called  it  "thyreophyma 
acutum,"  and  Baillie,  "inflammatio  glandulae  thyroideae."  Hedenus, 
Franck  and  Conradi  seem  to  have  realized  in  their  descriptions  of  the 
disease  that  there  was  a  difference  between  inflammations  of  a  normal 
thyroid  and  inflammations  of  a  goiter,  as  Conradi,  in  1824,  objected 
strenuously  to  the  name  "struma  inflammatoria"  applied  indifferently 
to  any  infectious  disease  of  the  thyroid.  In  1840  Weitenweber  fully 
appreciated  the  difference  between  the  two  conditions  and  called  inflam- 
mation of  the  normal  thyroid  "thyreo-adenitis,"  and  inflammation  of  a 
goiter  "struma  inflammatoria."  In  1857  Bauchet  published  a  very 
complete  article  on  both  forms  of  inflammation.  As  Conradi  did, 
Bauchet  also  considered  the  non-purulent  form  of  thyroiditis  as  the 
fore  stage  of  the  purulent  form.  In  1878  Kocher,  speaking  of  the 
etiology  of  infectious  diseases  of  the  thyroid,  made  a  great  step  forward 
in  claiming  that  all  inflammations  of  the  thyroid  were  of  a  metastatic 
nature;  and  the  correctness  of  such  views  was  demonstrated  bacterio- 
logically  by  Tavel  in  1892.  In  1895  Mvgind,  dividing  thyroiditis  into 
two  classes,  the  "simplex"  and  the  "suppurativa,''  claimed  that  the 
first  one  was  not  always  a  fore  stage  of  the  second,  but  was  in  many 
instances  a  disease  sui  generis.  Ewald,  in  1896,  although  admitting 
that  the  thyroiditis  simplex  might  be  of  "idiopathic  or  metastatic" 
origin,  did  not  recognize  for  it  an  entity  of  its  own,  bur  looked  upon 
the  non-suppurative  thyroiditis  as  the  fore  stage  of  the  purulent  form. 
The  same  was  done  by  von  Eiselsberg.      In   [894   De  Quervain,  in  an 


90  INFLAMMATIONS  OF  THE  THYROID 

eloquent  and  scientific  article,  took  up  this  question  again  and  shared 
entirely  Mygind's  views.  In  his  judgment  the  non-purulent  thyroiditis 
is  a  disease  sui  generis,  sharply  defined  clinically  as  well  as  pathologically. 

Before  discussing  these  views  let  us  have  a  clear  understanding  of 
the  terms  we  use.  We  call  thyroiditis  an  inflammation  of  a  normal 
thyroid  gland,  and  strumitis  an  inflammation  of  a  goiter,  no  matter 
what  its  variety  may  be.  When  we  speak  of  a  primary  thyroiditis  or  of 
a  primary  strumitis  we  mean  an  inflammation  which  apparently  seems 
to  occur  spontaneously  in  a  normal  thyroid  or  in  a  goiter;  nowhere  in 
the  organism  can  a  focus  be  found  which  might  explain  the  origin  of 
the  infecting  agent.  Secondary  thyroiditis  and  secondary  strumitis,  on 
the  other  hand,  are  infections  whose  infectious  agents  have  been  trans- 
ported metastatically  from  a  well-defined  infected  focus  in  the  body,  as 
pneumonia,  typhoid  fever,  etc.  Strictly  speaking,  however,  there  is  no 
such  thing  as  a  primary  infection  of  the  thyroid.  If  one  examines  care- 
fully and  critically  the  so-called  "primary  thyroiditis,"  or  "primary 
strumitis,"  it  will  always  be  found  that  the  patient  was  previously 
predisposed  to  infection  by  some  gastro-intestinal  disturbances,  some 
chronic  intoxications,  as  syphilis,  tuberculosis,  saturnism,  etc.  Thy- 
roiditis and  strumitis  are  all  of  metastatic  origin,  ergo,  secondary; 
nevertheless  we  shall  preserve  these  two  distinctions  for  the  sake  of 
convenience  and  clearness. 

We  distinguish  two  kinds  of  thyroiditis,  bacterial  and  toxic. 

Bacterial  Thyroiditis. — Bacterial  thyroiditis  is  caused  by  the  settle- 
ment of  the  microorganism  itself  in  the  thyroid;  toxic  thyroiditis  is  due 
to  the  inflammatory  reaction  of  the  thyroid  when  in  contact  with 
chemical  poisons  or  microbic  toxins  circulating  in  the  blood. 

I  cannot  bring  myself  to  consider  with  De  Quervain  and  Mygind 
the  non-purulent  form  of  bacterial  thyroiditis  as  a  class  apart,  a  disease 
sui  generis.  The  same  microorganism,  according  to  its  violence  on  one 
side,  and  the  means  of  defense  of  the  body  on  the  other,  will  in  one  case 
determine  only  a  non-purulent  thyroiditis;  whereas  in  another  case  it 
will  produce  suppuration.  Even  if  a  small  purulent  focus  has  started, 
it  may  not  necessarily  continue  to  evoluate  but  may  regress  and  finally 
be  absorbed.  Such  cases  will  be  catalogued  as  non-purulent  thyroiditis 
because  clinically  we  have  no  positive  means  of  distinguishing  the  puru- 
lent from  the  non-purulent  forms  in  their  incipent  stage.  In  that  respect 
very  instructive  is  the  case  reported  by  Breuer.  His  patient,  without 
any  apparent  cause,  was  taken  suddenly  sick  with  acute  thyroiditis 
developed  in  the  left  lobe  of  the  thyroid  gland.  Swelling,  local  and 
referred  pains,  difficulty  in  swallowing,  fever,  etc.,  were  present;  in  short, 
the  clinical  picture  was  identical  with  the  one  of  primary  non-purulent 
thyroiditis.      Four  or  five  days  afterward  everything  had  subsided,  but  in 


BACTERIAL  THYROIDITIS  91 

the  following  weeks  he  began  to  show  symptoms  of  exophthalmic  goiter, 
and  seven  months  afterward  died  from  the  consequences  of  this  disease. 
Postmortem  showed  in  the  left  lobe  a  small  encapsulated  abscess  which 
proved  to  be  of  staphylococcus  origin.  And  yet  this  case  had  been  labeled 
in  good  faith,  and  could  not  be  called  anything  else  than  "non-purulent 
thyroiditis." 

A  bacterial,  non-purulent  thyroiditis,  in  my  judgment,  is  only  a 
phase  of  a  process  whose  last  act  is  suppuration.  This  suppurative  stage 
may  or  may  not  be  reached;  we  have  no  means  to  know  beforehand, 
what  course  a  given  thyroiditis  will  take,  whether  abscess  will  form  or 
not.  This  is  certainly  true  in  typhoid,  diphtheria,  puerperal  infection, 
cholera,  influenza,  pneumonia,  and  erysipelas.  Therefore,  if  we  are 
willing  to  say  that  in  acute  thyroiditis  the  inflammatory  process,  accord- 
ing to  the  virulence  of  the  microorganism  and  the  individual  resistance 
of  the  patient,  may  never  go  further  than  the  non-purulent  stage,  and 
that  the  same  process,  when  conditions  of  virulence,  resistance,  etc.,  are 
changed,  may  pass  over  to  the  purulent  stage,  all  well  and  good  (the 
distinction  between  the  non-purulent  and  the  suppurative  stage  is 
needed  anyway  for  the  sake  of  clearness  in  describing  the  disease);  but 
to  make  of  the  non-purulent  stage  a  disease  sui  generis  does  not  seem  to 
me  rational.  It  might  be  permissible  to  put  under  this  separate  heading 
the  forms  of  thyroiditis  consecutive  to  infectious  diseases  whose  bac- 
terial etiological  factors  are  still  unknown,  as  in  scarlet  fever,  measles, 
parotitis,  and  acute  inflammatory  rheumatism;  these  forms  of  thyroid- 
itis do  not  suppurate.  As  we  do  not  know  if  in  such  circumstances 
thyroiditis  is  due  to  the  microbes  themselves,  too  mild  to  reach  the 
suppurative  stage,  or  to  their  toxins,  it  might  be  more  simple  and  non- 
committal to  regard  them  for  the  time  being  as  diseases  sui  generis, 
but  certainly  some  day  there  will  be  more  light  upon  this  subject,  and 
I  feel  confident  these  forms  of  acute  thyroiditis  will  be  classified  as  toxic 
forms  of  thyroiditis. 

According  to  the  foregoing  considerations  we  will  admit  that  bac- 
terial thyroiditis  may  evoluate  in  two  stages,  the  non-purulent  and  the 
suppurative  forms. 

Bacterial  thyroiditis  may  be  parenchymatous  or  interstitial.  In  the 
parenchymatous  form  the  epithelial  elements  are  mostly  involved,  whereas 
in  the  interstitial  form  the  connective  tissue  is  mostly  inflamed.  Bur,  as 
a  rule,  both  forms  of  thyroiditis  are  mixed  together,  one  predominating 
more  than  the  other. 

If  we  should  consider  a  goiter  as  the  result  of  an  infectious  process, 
the  goiter  in  itself  would  be  a  thyroiditis,  and  strumitis  would  then 
become  only  an  epiphenomenon  of  a  previous  infection.  Indeed,  one  can- 
not fail  to  see  there  must  be  a  connection  between  goiter  and   strumitis; 


92  INFLAMMATIONS  OF  THE  THYROID 

in  regions  where  goiter  is  endemic,  strumitis  is  mostly  found,  whereas 
thyroiditis  is  rare.     The  opposite  is  true  of  countries  free  from  goiter. 

One  of  the  greatest  laws  which  infections  seem  to  follow  with  predi- 
lection is,  they  localize  preferably  on  the  site  of  diminished  resistance. 
Now,  then,  as  we  know  that  in  all  infectious  processes  of  the  body  the 
thyroid  is  put  to  a  very  great  task,  being  seemingly  the  great  labora- 
tory where  the  products  of  thyroid  secretion  are  destined  to  neutralize 
or  render  harmless  the  poisons  of  metabolism,  it  is  not  illogical  to  admit 
that  after  a  long  illness  the  gland  is  in  a  state  of  exhaustion  and  becomes 
an  easy  prey  for  infection.  When  strumitis  occurs  in  cases  in  which 
acute  infection  has  apparently  not  previously  existed  somewhere  in  the 
body,  we  are  then  compelled  to  admit  that  goiterous  degeneration  has 
created  a  predisposition  to  infection.  Indeed,  goiter  with  its  degenera- 
tive and  hemorrhagic  processes  forms  a  suitable  "bouillon"  for  the  growth 
of  microorganisms  which  happen  to  be  wandering  in  these  regions. 

We  may  consequently  conclude  that  a  local  pathological  disposition 
of  the  thyroid  forms  a  locus  minor  is  resistentice,  and  thus  may  encour- 
age acute  inflammation  to  settle  in  the  thyroid.  The  mildest  degree  of 
local  disposition  is  found  in  thyroid  parenchymatous  hyperplasia,  but  as 
soon  as  thrombosis,  hemorrhages,  and  regressive  metamorphoses,  as 
fatty  and  colloid  degeneration,  take  place  the  local  disposition  of  the 
tissues  for  infection  is  greatly  increased.  This  is  so  true  that  typhoid 
bacilli,  in  order  to  be  able  to  produce  a  thyroiditis,  must  have  a  great 
virulence  or  they  must  develop  in  a  gland  already  degenerated.  Roger 
and  Gamier  were  unable  to  produce  experimental  thyroiditis  by  inject- 
ing typhoid  bacilli  in  the  thyroid  arteries  of  the  normal  gland  of  rab- 
bits. Traumatism  also  is  an  etiological  factor.  Of  course,  beside  local 
disposition,  the  virulence  of  the  microorganism  is  of  great  importance. 

Yet  we  must  say  there  are  in  the  body  very  few  organs  which  are 
less  susceptible  to  metastases  of  all  sorts  than  the  thyroid;  for  instance, 
metastases  in  that  gland  from  malignant  tumors  are  of  the  utmost 
rarity;  even  tuberculosis,  which  is  one  of  the  most  common  diseases, 
very  rarely  settles  in  the  thyroid.  Certainly,  this  relative  immunity 
must  not  be  an  accidental  one;  very  likely,  under  normal  conditions, 
the  thyroid  gland  has  a  powerful  bactericide  action,  capable  of  warding 
ofF  infections. 

If  it  is  a  well-accepted  fact  that  a  preexisting  goiter  is  a  predisposing 
factor  of  great  importance  in  the  etiology  of  strumitis,  what  about 
thyroiditis?  Is  there,  perchance,  a  small  goiterous  nodule  there  also, 
too  small  to  be  detected  clinically,  and  which  becomes  the  point  where 
infection  sets  in  ?    The  problem  is  not  easily  solved. 

We  really  have  no  means  to  decide,  clinically,  when  the  thyroid  ceases 
to  be  normal  and  begins  to  become  pathological.     Bassot,  in  postmortems 


ETIOLOGY  93 

of  pregnant  women  who  died  soon  after  deliver)',  found  the  thyroid 
three  or  four  times  larger  than  normally,  and  yet  in  many  of  these  cases 
the  histological  picture  was  one  of  a  normal  thyroid  gland.  De  Quer- 
vain  found  that  in  a  gland  weighing  50  gms.  or  more  the  histological 
picture  may  have  been  one  of  an  absolutely  normal  thyroid  gland, 
whereas  in  glands  weighing  between  20  and  30  gms.  unmistakable  signs 
of  diffuse  colloid  degeneration  might  be  seen.  Therefore  neither  weight 
nor  size  is  a  positive  criterion  when  it  comes  to  deciding  whether  the 
thyroid  gland  is  normal  or  not. 

Etiology. — Kocher  is  the  first  who  brought  light  into  the  etiology  of 
thyroiditis.  In  the  farsightedness  of  his  genius,  although  at  the  time 
he  did  not  have  bacteriology  to  support  his  theoretical  views,  he  claimed 
that  every  acute  thyroiditis  or  strumitis  was  due  to  metastasis  of  an 
infectious  agent  located  somewhere  in  the  organism,  or  originating  from 
the  intestinal  canal.  Later,  bacteriological  findings  proved  the  correct- 
ness of  such  views. 

Thyroiditis  and  strumitis  may  occur  spontaneously  without  any 
apparent  cause,  or  as  a  complication  of  another  infectious  process. 
They  happen  especially  during  convalescence  from  an  acute  illness,  and 
are  less  frequent  in  chronic  cases. 

Infection  may  take  place  in  three  different  ways:  (1)  by  contiguity. 
An  infection  localized  in  the  neighborhood,  as  for  instance,  in  the  case 
of  cervical  adenitis,  may  extend  gradually  over  to  the  thyroid;  this 
mode  of  infection  is  more  apt  to  cause  a  perithyroiditis  or  a  peristrumitis 
than  a  genuine  thyroiditis  or  strumitis;  however,  the  fact  is  possible, 
and  has  been  observed;  (2)  by  direct  inoculation,  as  in  a  puncture  with 
a  needle  or  an  injury  with  a  knife;  (3)  by  the  hematogenous  route.  As 
the  thyroid  has  no  excretory  canal  and  does  not  come  into  contact  with 
a  mucous  membrane  of  any  sort,  if  an  inflammation  sets  in,  and  if  the 
possibility  of  an  infection  by  direct  traumatism  or  by  propagation  from 
the  neighboring  tissues  has  been  excluded,  there  remains  only  one  pos- 
sible way  by  which  the  microorganism  might  have  traveled,  and  that  is 
by  the  hematogenous  route;  bacteria  thus  thrown  into  the  blood  current 
settle  in  the  thyroid. 

If  an  infected  focus  exists  somewhere  in  the  body,  thyroiditis  or 
strumitis  may  be  caused  by  the  direct  metastasis  of  the  same  micro- 
organism causing  the  primary  infection;  but  it  may  be  caused,  too,  by 
a  microorganism  of  an  entirely  different  nature  from  that  of  the  primary 
focus.     A  mixed  infection  may  even  be  present. 

The  number  of  microorganisms  incriminated  as  etiological  factors  oi 
thyroiditis  or  strumitis  is  a  very  large  one.  Osteomyelitis  and  metastatic 
meningitis  cannot  compete  with  thyroiditis  and  strumitis  so  far  as  the 
diversity  of  microorganisms  as  etiological  factors,      fhyroiditis  and  stru- 


94  INFLAMMATIONS  OF  THE  THYROID 

mitis  have  been  found  to  follow  not  only  pneumonia,  typhoid,  tonsil- 
litis, puerperal  infections,  gastritis,  enteritis,  pyemia,  but  also  scarlet 
fever,  diphtheria,  malaria,  influenza,  smallpox,  measles,  cholera,  dysen- 
tery, mumps,  and  inflammatory  rheumatism.  All  the  infections  of  the 
gastro-intestinal  tract  especially,  but  particularly  of  the  intestine,  have 
been  incriminated  in  the  production  of  thyroiditis.  The  microbes  mostly 
found  in  such  conditions  are  the  streptococcus,  the  staphylococcus,  the 
Bacillus  coli  in  pure  culture  or  associated  with  anaerobic  organisms. 
The  symbiosis  of  the  latter  microorganism  with  streptococcus  is  fre- 
quently found  in  gangrenous  thyroiditis.  Typhoid  bacilli  are  found, 
too,  as  etiological  factors  of  thyroiditis  and  strumitis.  Out  of  1700 
cases  of  typhoid  fever  Liebermeister  and  Hoffmann  found  15  cases  of 
thyroiditis  and  strumitis  with  six  abscesses. 

Pneumococcus  has  been  found  in  acute  infections  of  the  thyroid  fol- 
lowing pneumonia,  and  streptococcus  after  erysipelas  and  puerperal 
infection. 

As  said  before,  traumatism  may  be  an  adjuvant  etiological  factor  of 
great  importance  in  thyroiditis.  It  does  not  need  to  be  a  direct  injury 
of  the  thyroid,  as  a  puncture  with  a  needle  or  knife,  but  indirect  injury 
is  sufficient  to  cause  thyroiditis.  This  is  well  illustrated  in  the  case  of 
Schoninger,  who  reported  that  a  girl,  aged  three  years,  after  being 
attacked  and  nearly  choked  to  death,  developed  an  acute  thyroiditis. 
In  that  case  it  is  well  to  assume  that  a  hemorrhage  was  the  consequence 
of  the  direct  traumatism,  forming  in  that  way  an  excellent  "bouillon  of 
culture"  for  bacteria  to  grow  upon.  The  same  explanation  holds  true  in 
goiter.  Schoninger  reported  another  case  of  a  girl  who,  while  lifting  a 
heavy  weight,  felt  a  sharp  pain  in  the  region  of  the  thyroid,  and  soon 
after  developed  a  strumitis.  Similar  cases  of  thyroiditis  and  strumitis 
were  observed,  too,  by  Kocher  in  men  whose  profession  it  was  to  carry 
heavy  loads  on  their  heads  and  necks,  and  in  officers  of  the  army  whose 
duty  it  was  to  cry  out  loud  orders,  while  their  uniforms  fitted  their 
necks  tightly.  Cold  seems  to  have  been  in  some  cases  etiologically 
responsible  for  thyroiditis. 

Thyroid  inflammations  have  been  found  at  every  stage  of  life,  from 
the  young  child  to  the  old  adult.  Demme  saw  a  congenital  strumitis 
in  a  newborn  babe,  and  Berard  a  strumitis  in  an  old  man,  aged  seventy- 
five  years.  A  case  of  mine  was  in  a  woman,  aged  seventy  years.  But 
the  period  of  life  in  which  they  are  most  frequently  found  is  between 
fifteen  and  sixty  years.  Women  are  more  often  affected  than  men,  and 
this  may  be  explained  by  the  activity  of  their  sexual  apparatus.  Each 
period  of  their  genital  life,  as  puberty,  menstruation,  pregnancies, 
menopause,  is  an  occasion  for  congestive  reactions  in  the  thyroid,  and 
consequently  predisposes  to  goiter  development  and  infections. 


SYMPTOMS  95 

Pathology. — In  a  great  majority  of  cases  inflammation  is  localized 
to  one  lobe  while  the  rest  of  the  gland  remains  normal,  but  cases  have 
been  reported  in  which  infection  extended  to  both  lobes  and  the  isthmus. 
The  isthmus  and  the  pyramidal  process  are  less  frequently  involved. 

In  the  early  stage  of  the  development  of  the  infection,  namely,  in 
the  non-purulent  stage,  the  capsule  is  furrowed  with  distended,  partly 
thrombosed  veins;  the  glandular  tissue  is  extremely  congested,  dark 
red,  and  spangled  with  punctiform  hemorrhages.  In  places  small 
infarcts  are  seen.  Parenchyma,  as  well  as  interstitial  connective  tissue, 
is  involved.  Under  the  spur  of  the  infection  the  epithelium  begins  to 
proliferate;  the  cells  may  increase  in  size  and  number  to  such  an  extent 
as  to  become  multistratified  and  to  form  papillary  projections  into  the 
alveolar  lumen;  at  the  same  time  a  more  or  less  intense  cellular  des- 
quamation may  take  place.  The  colloid  becomes  vacuolated,  thinner, 
loses  its  staining  power,  and  in  many  alveoli  disappears  entirely.  The 
lymphatic  spaces  are  distended;  cells  of  connective-tissue  origin  pro- 
liferate; infiltration  with  leukocytes  is  more  or  less  marked. 

According  to  De  Quervain,  besides  these  elements  of  connective- 
tissue  origin  giant  cells  are  found  which  should  not  be  confused  with 
tuberculous  giant  cells.  They  are  seen  around  very  thick,  seemingly 
unabsorbable  lumps  of  colloid,  and  have  very  likely  a  phagocytic  action. 
They  are  the  same  ones  which  are  found  around  foreign  bodies,  and 
probably  have  the  same  significance. 

In  the  purulent  stage  suppuration  takes  place  in  one  or  more  of  the 
small  hemorrhagic  areas.  As  in  pyelonephritis  the  gland  may  become 
entirely  dotted  with  small  abscesses  which  may  remain  independent  ot 
each  other,  or  may  fuse  together  gradually,  forming  finally  a  large  puru- 
lent collection.  In  thyroiditis  the  abscess  is  never  very  large.  In  stru- 
mitis its  size  depends  upon  the  dimensions  of  the  preexisting  goiter,  and 
may  attain  large  dimensions,  especially  in  cystic  goiter. 

Pus  varies  in  consistency  and  color.  It  may  be  thick  or  thin,  yellow, 
brown  or  red,  according  to  the  amount  of  blood  which  it  contains  and 
to  the  nature  of  the  infecting  agent.  As  a  rule  it  is  found  serous,  brown- 
ish, and  hemorrhagic  in  streptococcus  infection;  thick  and  greenish  in 
pneumococcus  infection.  The  purulent  pouches  when  multiple  may 
communicate  or  may  not.  In  rare  instances  a  gas  due  to  gas-producing 
organisms  is  found  in  the  abscess. 

Symptoms.  The  clinical  aspect  of  thyroiditis  and  strumitis  varies 
with  the  previous  condition  of  the  patient  and  with  the  virulence  of  the 
microorganisms.  Clinically,  the  types  of  thyroiditis  and  strumitis  fol- 
lowing influenza,  typhoid,  cholera,  inflammatory  rheumatism,  pneumonia, 
and  erysipelas  do  not  differ  so  very  much  one  from  another.  I  hc\  have 
about  the  same  intensity,  the  same  course,  the  same  symptomatolog} . 
In   tonsillitis  and   malaria   they  seem   to  have  a   milder  course. 


96  INFLAMMATIONS  OF  THE  THYROID 

Pneumonic  thyroiditis,  as  a  rule,  takes  place  during  the  defervescing 
period  of  pneumonia,  evoluates  mildly,  has  very  little  tendency  to  sup- 
puration: if  it  suppurates,  the  signs  of  purulent  production  are  slow  to 
appear.  Acute  thyroiditis  develops  rarely  during  the  acute  period  of 
pneumonia.  However,  Vitello's  case  proves  that  this  is  possible, 
although  in  his  case  a  mixed  infection  was  present:  the  diplococcus  was 
associated  with  other  microorganisms. 

Typhic  thyroiditis,  too,  takes  place  during  the  convalescing  period, 
is  longer  in  its  evolution,  and  does  not  frequently  reach  the  suppurative 
stage.  Out  of  15  cases  of  thyroiditis,  Liebermeister  found  abscess  for- 
mations six  times.  Geza  Galli  reported  lately  a  very  remarkable  case 
of  strumitis  developed  twenty-one  years  after  the  patient  had  had  typhoid 
fever.  The  incised  abscess  proved  to  be,  bacteriologically,  a  pure  cul- 
ture of  typhoid  bacilli.  The  author  does  not  say  whether  the  patient 
was  a  typhoid  carrier. 

Puerperal  thyroiditis  occurs,  as  a  rule,  between  the  tenth  and  four- 
teenth day  from  the  beginning  of  the  infection. 

As  a  rule  in  thyroiditis  as  well  as  in  strumitis  the  debut  of  the  dis- 
ease is  very  sudden  and  is  frequently  accompanied  by  chills  and  high 
fever.  The  patient  complains  of  pain  in  the  region  of  the  thyroid,  with 
a  sensation  of  constriction  of  the  throat.  A  deep,  continuous,  and 
paroxystic  pain,  although  more  or  less  diffusely  distributed  over  the 
cervical  region,  is  most  marked  on  the  side  of  the  affected  lobe;  it  is 
exaggerated  by  pressure  and  by  movements  of  the  head,  especially  by 
extension,  which  compresses  the  gland  between  the  spinal  column  and 
the  superficial  cervical  muscles;  therefore  in  order  to  relax  these  muscles 
the  patient  holds  his  head  flexed.  The  pain  is  also  increased  by  the 
up-and-down  movements  of  the  larynx  during  the  act  of  swallowing; 
shooting  pains  never  fail  to  be  present  in  the  back  of  the  ear,  occipital 
region,  shoulder,  and  occasionally  in  the  lower  jaw.  These  referred 
pains  are  an  early  symptom,  and  are  complained  of  by  the  patient  long 
before  any  swelling  in  the  thyroid  is  noticed.  The  sensation  of  con- 
striction in  the  throat  is  due  to  mechanical  pressure  on  the  esophagus 
and  to  peri-esophageal  edema.  The  pain  in  swallowing  may  be  so 
intense  as  to  prevent  the  patient  from  taking  any  nourishment.  In 
later  stages,  especially  when  infection  is  localized  to  both  lobes,  the 
windpipe  is  compressed  and  may  be  displaced.  As  peritracheal  inflam- 
mation may  extend  to  the  mucous  membrane  of  the  windpipe  and  of 
the  larynx,  laryngotracheitis  accompanied  by  coughing  spells  takes 
place,  thus  increasing  the  dyspneic  symptoms,  which  may  become  very 
alarming,  because  in  thyroiditis  the  patient  has  not  had  time,  as  in 
simple  goiter,  to  get  used  to  the  diminished  caliber  of  the  windpipe. 

One  of  the  peculiarities  of  thyroiditis  is  its  liability  to  cause  marked 


SYMPTOMS  97 

cardiovascular  symptoms;  tachycardia  may  be  more  or  less  accentuated, 
heart  action  being  between  120  and  140.  What  strikes  the  attention  at 
once  is  the  disproportion  between  temperature  and  pulse-rate;  the  heart 
action  remains  rapid  even  if  the  temperature  is  not  elevated.  This 
tachycardia  becomes  more  accentuated  with  a  physical  effort,  but  may 
appear  without  any  cause,  and  is  then  liable  to  cause  the  most  annoying 
cardiac  palpitations.  It  is  of  thyrotoxic  origin.  Blood-pressure  is  low- 
ered and,  as  in  Parisot's  case,  may  be  so  low  as  to  cause  symptoms  of 
collapse,  which  may  become  very  alarming. 

These  cardiovascular  symptoms  follow  a  parallel  curve  with  the 
inflammation  of  the  thyroid,  reaching  their  maximum  when  the  phleg- 
masia is  at  its  highest  and  gradually  diminishing  with  the  retrocession 
of  the  inflammation.  As  a  rule  they  disappear  only  when  the  inflamma- 
tion of  the  gland  has  subsided  for  quite  a  long  time  before. 

Besides  these  manifestations,  symptoms  of  less  importance  may  be 
found,  as  hoarseness  due  to  involvement  of  the  inferior  laryngeal  nerve; 
sympathetic  symptoms  are  rare.  The  patient  complains  of  roaring  in 
the  ears  and  vertigo;  he  is  extremely  agitated  and  may  become  delirious. 
Nausea  and  vomiting  have  been  rarely  reported  and  they  have  been 
erroneously  attributed  to  pressure  on  the  pneumogastric  nerves.  They 
are  most  likely  of  thyrotoxic  origin. 

Fifteen  to  twenty  hours  after  the  debut  of  the  infection  a  diffuse 
swelling  located  between  the  sternocleidomastoid  muscles  makes  its 
appearance.  It  is  closely  related  to  the  larynx  and  goes  up  and  down 
with  it  during  deglutition.  In  a  great  many  instances  the  swelling 
involves  one  lobe,  and  in  some  others  it  may  be  found  extending  over 
both  lobes,  one  side  being  more  swollen  than  the  other.  The  isthmus 
and  processus  pyramidalis  are  seldom  involved.  If  the  gland  was  previ- 
ously absolutely  normal,  the  size  of  the  swollen  lobe  will  not  exceed  that 
of  an  egg.  Of  course,  if  there  was  previously  a  goiter,  then  the  size  of 
the  swollen  lobe  will  vary  accordingly. 

The  tumor,  especially  in  early  development,  is  hard  in  consistency. 
The  veins  of  the  neck  are  dilated;  the  patient's  face  is  congested  and 
may  become  cyanotic;  the  region  of  the  thyroid  is  swollen,  hot,  and 
tense;  in  some  instances  infiltration  of  the  cervical  region  may  become 
so  marked  that  it  is  no  longer  possible  to  outline  the  limits  of  the 
thyroid;  a  diffuse,  board-like  wall  covers  the  entire  region  of  the  neck. 
Palpation  must  be  done  very  carefully,  as  it  is  exceedingly  painful  and 
may  provoke  suffocating  spells. 

Objective  as  well  as  subjective  symptoms  increase  very  rapidly  t<>i 

;i  few  days  until  they  reach  their  maximum;  if,  then,  thyroiditis  remains 

in  the  non-purulent  stage,  it  subsides  rapidly  and  disappears  in  a  f(  \\ 

days  or  in  two  or  three  weeks.     According  to   Ewald   the   non-purulent 

7 


98  INFLAMMATIONS  OF  THE  THYROID 

form  is  found  in  25  per  cent,  of  the  cases  of  acute  inflammation  of  the 
thyroid.  In  some  instances,  after  a  period  of  rapid  amelioration,  the 
disease  retrocedes  more  slowly  and  may  be  protracted  over  a  period  of 
several  weeks.  The  gland  may  recover  its  previous  normal  condition, 
or  a  few  indurated  areas,  which  in  time  will  be  converted  into  fibrous 
goiters,  may  be  left  as  the  only  living  witnesses  of  the  past  phlegmasia. 
Exceptionally,  after  a  remission  of  a  few  days,  if  the  infection  has  been 
confined  to  one  lobe  only,  the  opposite  side  may  become  involved  and 
acute  symptoms  begin  all  over  again. 

But  in  many  instances  the  infection  instead  of  retroceding,  progresses 
until  an  abscess  is  formed.  The  skin  becomes  more  and  more  red  and 
swollen  until  fluctuation  becomes  manifest.  If  the  abscess  is  not  incised, 
it  mav  open  spontaneously  outside,  leaving  a  fistula  which  may  last 
quite  a  long  time — seven  years  in  P.  Franck's  case.  In  some  instances 
the  abscess  may  rupture  into  the  trachea  and  the  esophagus.  Death  is 
not  necessarily  the  consequence  of  such  an  accident,  as  cases  have  been 
reported  in  which,  after  spontaneous  rupture  of  the  abscess  into  the 
trachea,  recovery  was  uneventful.  If  the  abscess  fuses  downward  into 
the  mediastinal  space,  it  causes  a  diffuse,  purulent  mediastinitis  which  is 
most  invariably  fatal. 

In  some  rare  cases  of  thyroiditis  called  by  Lebert  thyroiditis  dissecans, 
a  portion  of  the  thyroid  gland  is  found  spontaneously  severed  from  the 
body  of  the  gland,  soaked  in  a  fetid,  reddish  serosity  similar  to  the  one 
found  in  phlegmon.  This  glandular  sequestrum  swims  loosely  in  the 
purulent  cavity;  it  is  often  formed  by  colloid  nodules,  showing  that 
instead  of  a  thyroiditis  we  have  in  reality  a  strumitis. 

Similar  cases  have  been  reported  by  Lowenhardt,  Kern,  Knuppel, 
Eulenberg  and  Middledoiff,  and  considered  as  acute  massive  gangrene 
of  the  thyroid.  The  special  cause  of  such  powerful  infections  must 
certainly  be  looked  for  in  the  malignant  virulence  of  microbes  such 
as  streptococcus  and  anaerobic  bacilli  of  putrefaction. 

Besides  these  acute  forms  of  gangrene  there  are  others,  less  obstrep- 
erous, less  dangerous  quoad  vitam,  but  very  much  more  unpleasant  on 
account  of  their  long  duration.  They  are  infections,  occurring  in  old 
goiters  with  fibrous  or  calcareous  nodules  whose  blood  supply  is  precari- 
ous, and  consequently  are  soon  isolated  from  the  gland  and  converted 
into  foreign  bodies.  As  soon  as  surgical  or  spontaneous  drainage  is  estab- 
lished, suppuration  does  not  stop  until  total  elimination  of  the  foreign 
body  has  occurred,  and  this  may  take  months  or  years. 

Diagnosis. — Inspection  and  palpation  of  the  cervical  region  are  so 
easy  there  should  be  no  difficulty  in  making  the  correct  diagnosis.  If 
there  is  any  doubt  left,  the  up-and-down  movements  of  the  larynx  will 
clear   up  the  question;  the  latter  symptom  is  always  present  except  in 


DIAGXOSIS  99 

cases  in  which  inflammation  has  become  so  far  advanced  that  a  diffuse 
infiltration  extends  all  over  the  neck. 

Congestion,  especially  in  women,  is  not  an  uncommon  feature  at  the 
time  of  their  menstruation  or  pregnancy,  but  in  such  cases  pain,  fever, 
and  all  the  other  general  symptoms  found  in  acute  thyroiditis  will  fail 
to  be  present.  If  a  sensation  of  constriction  in  the  throat,  and  even 
respiratory  disturbances,  are  complained  of,  it  will  not  be  difficult  to 
put  them  in  relation  with  some  nervous  and  hysterical  condition  of 
the  patient  unless  a  goiter  large  enough  to  satisfactorily  explain  these 
symptoms  should  be  present. 

It  may  become  extremely  difficult  to  differentiate  a  hemorrhage  tak- 
ing place  in  a  goiter  from  a  strumitis.  Spontaneous  hemorrhages  are 
very  rare  in  a  normal  thyroid,  whereas  they  are  often  seen  in  goiter. 
Hemorrhage  may  take  place  in  a  nodule  which  is  so  small  that  the  patient 
is  unaware  of  its  presence,  and  yet  such  swelling  may  cause  an  enlarge- 
ment of  the  entire  lobe,  so  that  the  pathological  picture  may  be  mis- 
taken for  thyroiditis.  The  history  and  development  are  of  great  value 
in  differentiating  inflammation  from  hemorrhage.  If  acute  swelling  of 
the  thyroid  has  taken  place  in  connection  with  some  infectious  process, 
the  probability  will  be  in  favor  of  thyroiditis,  but  if  the  swelling  has 
no  relation  whatsoever  with  an  infectious  process,  and  perchance  has 
appeared  after  a  physical  effort  or  traumatism,  it  will  be  reasonable  to 
admit  that  we  have  to  deal  with  a  hemorrhage.  Local  pain  and  fever, 
although  possibly  present  in  hemorrhage,  are  less  marked  than  in  acute 
infection,  and  when  present  complicate  that  much  more  the  diagnosis, 
as  in  the  following  case  of  mine.  A  young  woman,  aged  eighteen  years, 
had  a  small  goiter  for  which  she  was  being  treated  by  an  osteopath. 
After  severe  manipulations  of  the  neck  she  complained  of  pain  and  sen- 
sation of  constriction  in  the  cervical  region.  The  right  lobe,  in  which 
goiter  was  developed,  had  increased  rapidly  in  size  and  was  very  painful 
to  pressure.  The  temperature  was  ioi°;  the  skin  of  the  neck  was  warm 
but  not  infiltrated.  After  three  days  everything  subsided,  but  the  goi- 
ter remained  a  little  larger  than  before.  In  this  case,  after  some  hesita- 
tion, I  made  the  diagnosis  of  hemorrhage  in  a  colloid  goiter  following 
traumatism.  As  the  patient  did  not  consent  to  an  operation  at  any  time 
I  never  had  the  opportunity  to  confirm  my  diagnosis,  although  in  all 
probability  it  was  correct. 

In  conclusion  we  may  say  that  in  hemorrhage  the  symptoms  reach 
their  climax  more  rapidly  and  subside  more  quickly  than  in  thyroiditis. 

To  mistake  acute  thyroiditis  for  tuberculosis  or  syphilis  is  hardly 
possible.  Miliary  tuberculosis  of  the  thyroid  is  only  an  incident  of  a 
more  important  process,  namely,  generalized  miliary  tuberculosis;  there- 
fore  it   has    no   clinical    interest,   and    is,   as   a    rule,  a    postmortem    find- 


100  INFLAMMATIONS  OF  THE  THYROID 

ing.  Small  localized  tuberculous  foci  might  be  confused  with  thyroid- 
itis, but  their  chronic  character  and  the  lack  of  general  symptoms  will 
afford  the  correct  diagnosis.     The  same  is  true  of  syphilis. 

Differential  diagnosis  between  strumitis  and  malignant  goiter, 
although,  as  a  rule,  without  difficulty,  is  sometimes  not  easy.  For  instance, 
a  rapidly  growing  sarcoma  has  been  mistaken  for  an  acute  infection 
more  than  once,  because  in  such  instances  the  symptoms  have  been 
very  much  the  same.  The  skin  may  be  warm,  red,  infiltrated,  painful  to 
pressure,  and  even  fever  may  be  present.  I  saw  in  Charleston,  W.  Va., 
a  man,  aged  forty-five  years,  a  foreigner  speaking  not  a  word  of  English, 
French,  German,  or  Italian,  so  that  it  was  impossible  for  me  to  get  any 
information  so  far  as  the  history  of  his  case  was  concerned.  In  the  right 
lobe  was  found  a  large  tumor  with  diffuse  limits;  very  adherent  to  the 
neighboring  tissues;  scarcely  sensitive  to  pressure  and  firm  in  consis- 
tency. Yet  on  deep  pressure  there  was  a  sensation  of  elasticity.  The 
skin  was  infiltrated  and  red;  he  had  no  temperature.  Although  the 
patient  had  become  very  emaciated,  he  looked  to  me  as  being  pro- 
foundly toxic  rather  than  cachectic,  and  despite  the  diagnosis  of  malig- 
nant tumor  made  by  several  other  physicians,  I  concluded  the  patient 
was  suffering  from  a  slow-developing  strumitis,  and  advised  operation, 
which  later  confirmed  the  correctness  of  my  views. 

On  account  of  the  difficulty  in  swallowing,  and  because  of  the  pain 
and  sensation  of  constriction  in  the  throat,  non-purulent  thyroiditis 
might  be  confused  with  tonsillitis,  but  an  intrabuccal  examination  will 
settle  the  matter.  An  acute  cervical  adenitis  might  be  mistaken  for 
thyroiditis  or  strumitis,  but  their  localization  and  anatomical  relations 
with  the  other  organs  of  the  neck  will  soon  throw  some  light  upon  the 
subject.  In  the  diffuse  cervical  phlegmon  the  inflammation  is  more 
superficial;  the  infiltration  is  more  diffuse  and  deglutition  is  less  painful. 
In  rare  instances  a  mistake  might  be  possible  with  laryngochondritis. 

It  is  not  only  of  theoretical  interest  to  decide  if  in  a  given  case  we 
have  to  deal  with  thyroiditis  or  strumitis,  but  it  is  also  important  from 
the  prognostic  point  of  view.  Experience  shows  that  thyroiditis  is  more 
apt  to  be  non-purulent,  whereas  strumitis  will  terminate  by  suppura- 
tion. Consequently,  not  only  the  duration  but  the  course  of  the  disease 
and  the  dangers  connected  with  it  may  be  predicted  to  the  patient  or 
his  family. 

In  order  to  decide  if  we  have  to  deal  with  a  thyroiditis  or  strumitis 
the  history  of  the  case  will  be  of  great  assistance,  as  it  will  indicate 
whether  the  patient  has  previously  had  a  goiter  or  not.  If  the  patient 
lives  in  a  country  where  goiter  is  endemic,  not  too  much  stress  should 
be  placed  upon  his  answer  if  negative,  as  the  chances  are  great  that  his 
thyroid  might  contain  a  few  unobserved  goiterous  nodules.     This  is  so 


PROGXOSIS  101 

true  that  Kocher  saws  he  has  never  seen  a  case  of  genuine  thyroiditis. 
All  the  acute  cases  which  came  under  his  observation  were  developed 
in  an  already  degenerated  thyroid. 

The  size  of  the  swelling  is  of  good  differential  diagnostic  value.  In 
thyroiditis  the  tumor  rarely  exceeds  the  size  of  an  egg,  whereas  in  stru- 
mitis the  size  will  depend  upon  the  volume  of  the  goiter.  In  thvroid- 
itis,  infection  involves  from  the  start  the  entire  lobe.  Strumitis,  even 
if  developed  in  a  small  nodule,  remains  for  a  time  localized  to  this 
nodule;  only  later  the  inflammatory  processes  extend  to  the  entire  lobe. 
If  inflammation  involves  both  lobes,  the  chances  are  that  we  have  to 
deal  with  a  thyroiditis,  or  if  one  lobe  is  affected  and  after  subsiding  the 
inflammatory  symptoms  appear  on  the  other  side  the  chances  are  that 
we  have  to  deal  with  a  thyroiditis. 

Prognosis. — The  prognosis  of  acute  infection  of  the  thyroid  depends 
very  much  upon  the  virulence  of  the  microbes  and  upon  the  condition 
of  the  patient  at  the  time  the  infection  takes  place. 

If  suppuration  does  not  take  place,  the  inflammatory  symptoms 
subside  rapidly;  sometimes  even  small  abscesses  regress  spontaneously, 
but,  as  a  rule,  if  suppuration  sets  in,  the  process  will  go  on  until  spon- 
taneous or  surgical  drainage  has  taken  place.  During  this  period  the 
inflammatory  process  may  endanger  the  life  of  the  patient  on  account 
of  the  septicemic  phenomena  due  to  resorption  of  infectious  materials 
taking  place  as  long  as  the  abscess  under  tension  has  not  been  opened. 
It  may  endanger  life  on  account  of  pressure  symptoms  causing  asphyxia, 
and  on  account  of  a  possible  perforation  into  the  trachea,  esophagus, 
pleura,  and  mediastinal  space.  The  dangers  of  suffocation  cannot  be 
better  illustrated  than  in  the  case  of  P.  Franck.  When  he  was  a  mere 
boy  he  was  taken  ill  with  strumitis.  The  dyspneic  symptoms  became 
so  alarming  that  the  life  of  the  child  was  in  danger.  The  best  physician 
in  the  neighborhood,  called  in  to  see  the  young  patient,  declared  pom- 
pously that  "a  nerve  in  the  child's  neck  had  been  ruptured,"  and  that 
death  was  imminent.  The  mother,  who  had  more  medical  "horse-sense" 
than  all  the  medical  academy  of  that  time,  thought  that  the  swelling 
in  the  neck  had  something  to  do  with  the  choking  of  her  child.  She 
called  in  the  barber  of  the  corner  and  told  him  to  make  an  incision  with 
his  razor  in  the  swelling.  The  barber  did  so,  and  at  once  a  Stream  oi 
pus  rolled  out,  the  dyspneic  symptoms  ceased,  and  so  was  saved  the 
life  of  P.  Franck,  who  at  the  beginning  of  the  nineteenth  century  became 
a  surgeon  of  great  repute.  As  a  result  of  this  incision  a  fistula  remained 
for  seven  years  before  closing  spontaneously. 

So  far  as  death  is  concerned,  non-purulent  th\  roiditis  is  very  much 
less  dangerous  than  the  purulent  form.  According  to  Robertson  s  sta- 
tistics,  12  out  of  96  cases  died;  ^4  were  non-purulent  thyroiditis,  with  2 


102  INFLAMMATIONS  OF  THE  THYROID 

deaths;  41  were  purulent,  with  9  deaths;  1  was  gangrenous,  with  1 
death.  It  seems,  however,  that  with  our  present  knowledge  of  surgery 
that  the  death-rate  ought  to  be  reduced. 

A  serious  and  frequent  sequelae  of  thyroiditis  is  the  development  of 
exophthalmic  goiter. 

Treatment. — In  non-suppurative  thyroiditis  the  treatment  will  differ 
according  to  the  infecting  agent;  for  instance,  rheumatic  thyroiditis  will 
be  amenable  to  treatment  with  sodium  salicylate;  thyroiditis  consecu- 
tive to  malaria  will  be  greatly  benefited  by  quinine;  thyroiditis  due  to 
influenza  will  also  derive  benefit  from  salicylate.  For  the  other  forms  of 
thyroiditis  we  have  no  specific  remedies;  the  treatment  must  be  symp- 
tomatic. As  a  rule  we  might  say  that  in  every  form  of  thyroiditis,  except 
the  malarial  form,  salicylate  should  be  used  because  many  of  such  acute 
cases  seem  to  be  in  relation  with  some  rheumatic  condition.  As  non- 
suppurative thyroiditis  subsides  spontaneously  no  surgical  interference 
will  have  to  be  considered  unless  the  inflammation  should  have  taken 
place  in  a  diffusely  enlarged  parenchymatous  or  colloid  gland  causing 
dyspneic  symptoms.  In  that  case  the  surgeon  may  be  called  upon  to 
perform  a  tracheotomy  or,  better,  thyroidectomy. 

When  the  abscess  is  formed,  it  must  be  opened  and  drained,  and  by 
the  way,  it  is  not  always  easy  to  tell  whether  the  abscess  is  present  or 
not.  Fluctuation,  which  is  really  about  the  only  reliable  sign  betraying 
the  presence  of  pus,  is  not  always  detectable  because  the  abscess  may  be 
deeply  situated  and  surrounded  by  a  hard,  thick  capsule  of  peristru- 
mitis, or  because  small  abscesses  may  be  difFusely  spread  throughout  the 
gland,  so  that  if  one  should  wait  for  fluctuation  to  appear  before  inter- 
fering surgically,  he  might  overlook  the  psychological  moment  for 
operation  and  thus  allow  his  patient  to  run  undue  risks  so  far  as  compli- 
cations and  death  are  concerned.  On  the  other  hand,  one  might  be  so 
misled  as  to  take  a  pseudofluctuation  for  a  real  one,  and  on  the  strength 
of  such  findings  may  be  induced  to  operate,  expecting  to  find  an  abscess. 
Great  will  be  his  surprise  to  find  only  a  much-congested  gland. 

Very  suggestive  of  abscess  formation  will  be  the  fact  that  inflam- 
mation is  no  longer  localized  to  the  lobe  itself,  but  has  extended  difFusely 
to  the  neighboring  tissues.  Very  suggestive,  too,  of  an  abscess  forma- 
tion is  the  presence  of  a  very  hard  lobe  whose  central  portion  seems  to 
be  soft.  The  blood  count  and  temperature  may  be  of  help,  as  in  non- 
suppurative thyroiditis  temperature  climbs  gradually,  and  when  it  has 
reached  its  climax,  gradually  comes  down  in  lysis,  whereas  in  abscess 
formations  the  temperature  remains  high  and  takes  a  septic  curve. 

It  would  be  a  mistake  to  rely  upon  an  exploratory  puncture  as  a 
means  of  deciding  whether  the  abscess  has  formed  or  not,  because  if 
the  puncture  is  negative,  it  does  not  mean  that  pus  is  not  present,  but 


TOXIC  THYROIDITIS  103 

means  only  that  the  needle  did  not  strike  the  purulent  pouch  or  that 
the  pus  is  too  thick  to  be  aspirated.  If  symptoms  are  so  alarming  as 
to  necessitate  an  immediate  operation  the  exploratory  puncture  only 
means  precious  time  lost.  If  they  are  not,  there  will  be  enough  time 
left  to  make  a  correct  diagnosis  without  endangering  the  life  of  the 
patient  by  an  exploratory  puncture,  because  this  puncture  is  bv  no 
means  a  harmless  one.  It  may  determine  a  sudden  hemorrhage  into  the 
goiter  and,  consequently,  cause  severe  choking  spells  in  a  very  short 
time.  Hence  the  following  rule:  If  at  any  time  one  wishes  to  make  an 
exploratory  puncture,  everything  should  be  in  readiness  for  an  immediate 
subsequent  operation  if  it  should  become  necessary. 

In  conclusion  we  may  say  that  the  diagnosis  of  abscess  cannot 
always  be  made  with  certainty,  and  that  it  is  better  to  operate  a  little 
too  soon  than  too  late.  If  the  abscess  is  still  very  well  encapsulated,  and 
if  the  infiltration  with  the  neighboring  tissues  is  not  such  as  to  render 
the  operation  extremely  difficult,  the  removal  of  the  tumor  in  toto  is 
the  most  feasible  thing  to  do;  but  if  for  some  reason  or  another  the  sur- 
geon must  be  parsimonious  with  the  thyroid  tissue,  as  in  a  case  of  bilat- 
eral thyroiditis,  incision  of  the  purulent  pouch  and  drainage  is  the  logi- 
cal procedure.  It  is  nearly  impossible  to  set  down  hard-and-fast  rules, 
as  indications  will  vary  with  each  given  case.  Judgment  and  experience 
will  be  the  surgeon's  best  guides. 

Toxic  Thyroiditis. — As  we  have  a  toxic  hepatitis  and  a  toxic  nephri- 
tis, so  we  have  also  a  toxic  thyroiditis.  It  is  caused  by  chemical  poisons 
and  bacterial  toxins,  whereas  the  bacterial  thyroiditis  is  caused  by  the 
microorganism  itself.  Experimentally,  it  has  been  very  well  demon- 
strated that  chemical  poisons  such  as  phosphorus,  nitrate  of  silver, 
iodin,  turpentine,  and  pilocarpine  cause  a  toxic  thyroiditis  characterized 
histologically  by  hyperplasia,  degeneration,  and  desquamation  of  the 
epithelium  and  sometimes  by  increase,  but  more  often  diminution  or 
absence  of  colloid,  and  more  or  less  marked  hyperemia.  As  a  rule 
leukocyte  infiltration  is  less  frequent  than  in  bacterial  thyroiditis.  In 
nicotine  and  lead  poisoning  no  alterations  are  present.  Although  mostly 
absent,  swelling  in  such  toxic  conditions  may  be  more  or  less  marked; 
it  is  a  well-known  fact  that  acute  lodism  may  be-  followed  by  acute 
swelling  and  inflammation  of  the  parotids.  The  same  may  be  true  for 
the  thyroid  as  in  Lublinski's  case-,  in  which  the  thyroid  became  swollen 
and  inflamed  during  treatment  with  K.I.  Ever)  symptom  subsided 
after  the  medicament  was  discarded. 

When  once  it  was  found  that  the  thyroid  was  so  susceptible  ro  chem- 
ical poisons  it  was  only  logical  to  conclude  thai  bacterial  toxins  mighl 
have  the  same  effect  upon  that  organ,  hence  the  experiment  undertaken 
by  Roger  and  Gamier,  Crispino,   lorn,  De  Quervain  and  others,     fhey 


104  INFLAMMATIONS  OF   THE  THYROID 

found  that  the  introduction  ot  bacterial  toxins  into  the  general  as  well 
.  s  into  the  thyroid  circulation  had  on  the  thyroid  about  the  same  influ- 
ence as  the  chemical  poisons,  as  hyperemia,  proliferation,  and  desquam- 
ation of  the  epithelium,  diminution  or  absence  of  colloid  and  its  increase 
in  the  lymphatic  vessels.  According  to  De  Ouervain  a  pure  culture  of 
a  virulent  microorganism  injected  into  the  artery  of  the  thyroid  may 
ss  through  the  thyroid  without  leaving  any  marks  of  its  passage,  but, 
on  the  other  hand,  may  cause  disparition  of  the  colloid,  desquamation 
of  the  epithelium,  and  the  appearance  of  polynuclear  leukocytes  in  the 
alveoli. 

After  these  findings  it  became  evident  that  a  step  further  should  be 
made  and  that  the  relations  between  thyroid  and  infectious  diseases 
in  man  should  be  thoroughly-  investigated.  Sokolow  was  the  first  who, 
in  1896,  tried  to  work  out  these  relations.  He  tound  that  in  acute  dis- 
s,  fatty  degeneration  ot  the  follicular  epithelium  with  desquama- 
tion took  place.  M tiller  in  the  same  year  reported  about  the  same 
findings.  In  1900  Roger  and  Gamier  reported  the  result  of  the  examina- 
tion ot  forty  thyroid  glands  which  had  been  taken  from  patients  who 
had  died  from  measles,  scarlet  fever,  diphtheria,  acute  gastro-ententis, 
typhoid,  cerebrospinal  meningitis,  peritonitis,  rabies,  and  smallpox,  and 
in  nearly  every  case  they  tound  marked  histological  changes  in  the 
thyroid.  Even  diffuse  hemorrhages  were  present  in  three  cases.  In 
some  instances  the  epithelium  had  proliferated  to  such  an  extent  as  to 
form  papillary  formations  projecting  into  the  alveolar  lumen.  The 
cellular  protoplasm  was  tound  granular,  nuclei  were  swollen  and  stained 
with  difficulty.  Hand  in  hand  with  proliferation  a  cellular  desquamation 
was  noticed.  The  colloid,  thin  in  places,  was  absolutely  absent  in 
others.  The  interstitial  connective  tissue  showed  very"  little  pathological 
changes  except  in  thyroids  of  patients  who  had  died  from  tuberculosis. 
In  such  instances  the  authors  found  a  diffuse  sclerosis  of  the  thyroid, 
the  alveoli  being  choked  by  the  increased  connective  tissue.  In  their 
opinion  this  sclerotic  process  was  the  result  of  tuberculous  toxins.  They 
concluded  that  in  infectious  diseases,  according  to  the  gravity  and 
duration  ot  the  infectious  process,  after  a  period  of  functional  stimula- 
tion leading  to  hyperthyroidism  symptoms,  the  thyroid,  injured  by  per- 
tent  and  deleterious  irritations  of  toxic  nature,  may  finally  be  put  in 
a  state  ot  more  or  less  complete  functional  inhibition;  hence  hypothy- 
roidism.    Torri  shared  the  same  v'u 

Kashiwamura,  in  i^ci,  relating  the  results  of  his  investigations 
on  53  thyroids  from  patients  dead  from  various  infectious  diseases, 
tried  to  disprove  the  findings  of  B  ger,  Gamier  and  Torri.  He  did  not 
find  the  same  typical  changes  described  in  the  epithelium,  colloid  and 
connective  tissue,  and  concluded  that,  owing  to  the  fact  that  the  physi- 


TOXIC  THYROIDITIS  105 

ognomy  of  the  thyroid  is  already  so  variable  in  normal  conditions,  it 
would  not  be  safe  to  draw  conclusions  derived  solely  from  its  histolog- 
ical appearance;  in  other  words,  it  is  difficult  to  decide  what  belongs  to 
the  normal  histology  and  what  belongs  to  pathology.  De  Quervain, 
Crispino.  Sarbach,  Serrafini,  Vitry  and  Giraud.  on  the  other  hand,  found 
that  a  manifest  relation  between  the  thyroid  and  infectious  diseases 
exists,  and  according  to  their  researches  the  pathological  changes  are 
mostly  in  proportion  to  the  severity  of  the  disease.  De  Quervain,  in 
ti  gating  the  condition  of  the  thyroid  in  45  cases,  in  which  the  cause  of 
death  was  tuberculosis,  cancer,  cardiac,  liver  and  kidney  diseases,  peri- 
tonitis, puerperal  infection,  diabetes,  scarlet  fever,  smallpox,  measles, 
diphtheria,  typhoid,  and  pneumonia,  found  changes  in  the  epithe- 
lium characterized  by  proliferation,  desquamation,  fatty  degeneration 
of  the  desquamated  cells,  thinning,  diminution  or  absence  of  colloid, 
increased  vascularization  in  the  gland  in  toto,  and  some  pathological 
changes  of  the  connective  tissue  with,  in  certain  cases,  leukocyte  infil- 
tration. In  patients  who  died  from  cancerous  cachexia,  diabetes,  neph- 
ritis. Addison's  disease,  and  uremia  no  pathological  changes  of  the  thy- 
roid were  detected.  S  a  roach's  conclusions,  after  investigating  67  cases, 
were  as  follows: 

1.  Acute  infections  may  produce  in  the  thyroid,  histological  altera- 
tions, characterized  by  increase  in  size  and  in  number  of  the  alveolar 
cells,  their  desquamation  and  degeneration,  liquefaction  and  diminu- 
tion of  the  colloid,  and  hyperemia.  The  connective  tissue  remains 
intact. 

:     Alcoholism  can  determine  similar  alterations  in  the  gland. 

Chi  :>nic  pulmonary  tuberculosis  produces  a  sclerosis  of  the  thyroid 
with  secondary  atrophy  of  the  alveoli. 

4.  Nephritis,  uremia,  cancerous  cachexia,  and  sarcoma  do  not 
produce  any  alterations  of  the  thyroid. 

rr  and  Esmonet,  treating  the  epithelium  of  the  thyroid  with  osmic 
methods,  tound  that  normally  the  epithelium  is  exempt  from  fatty 
degeneration,  whereas  in  infections  and  cachectic  conditions,  as  in  cancer. 
leukemia,  and  tuberculosis,  the  epithelial  elements  have  undergone  a 
marked  fatt  _  neration.     Finally,  Gregor,  in  26  thyroids  of  children 

who  had  died  of  scarlet  fever,  tound,  too,  the  same  pathological  char  _ 
reported  by  all  authors. 

Consequently,  from  all  this  wide  and  carefully  conducted  research 
work  \vc  can  safely  conclude  that  the  thyroid  does  not  remain  indifferent 
in  the  presence  of  the  important  pathological  phenomena  taking  place 
in  the  organism.  It  reacts  more  or  less  constantly  to  even-  infectious 
process  by  some  degree  of  hyperplasia  which  is  often  clinically  deu 
able.     It  is  then  know:  -Kptom. 


106  INFLAMMATIONS  OF   THE  THYROID 

The  question  arises  whether,  in  a  given  case,  we  have  to  deal  with 
a  bacterial  thyroiditis  or  a  toxic  one,  and  I  must  say  that  the  differ- 
entiation between  the  two  is  certainly  not  easy.  We  might  say  that  in 
toxic  thyroiditis,  as  the  entire  gland  is  flooded  with  toxins,  the  damages 
will  be  diffuse  and  spread  all  over  the  gland.  Furthermore,  as  the  toxins 
are  diluted  in  the  blood,  their  damaging  power  being  diminished,  patho- 
logical changes,  except  in  severe  intoxication,  will  be  more  or  less  mild. 
Consequently,  the  immediate  clinical  symptoms  will  be  much  less  marked 
than  in  bacterial  thyroiditis,  and  swelling  of  the  thyroid  may  not  be 
present  at  all,  although  a  slight  enlargement  may  easily  escape  unnoticed. 
In  that  respect  the  researches  of  Gamier  are  extremely  interesting. 
Taking  systematically  the  measurements  of  the  neck  in  20  cases  of 
scarlet  fever  he  found  that  mil  cases  the  circumference  of  the  neck  was 
increased  from  1  to  2  cms.,  yet  no  clinical  symptoms  were  present. 
Very  likely  if  more  attention  should  be  given  to  this  phase  of  the  ques- 
tion we  should  find  that  Vincent's  thyroideal  symptom  in  infectious 
diseases  is  present  more  often  than  we  think. 

If  toxic  thyroiditis  has  a  less  noisy  symptomatology  and  pathology 
than  bacterial  thyroiditis,  it  does  not  follow  that  it  is  a  harmless  occur- 
rence, as  this  form  of  thyroiditis  seems  preferably  to  injure  the  physi- 
ological function  rather  than  the  anatomical  elements  of  the  thyroid. 
Frequently  there  is  found  an  acute  Graves'  disease  grafted  upon  a  seem- 
ingly innocuous  infection,  as  tonsillitis,  etc.  Even  myxedema  has  been 
the  consequence  of  such  toxic  conditions. 

Tuberculosis  of  the  Thyroid. — It  is  classical  to  say  that  tuberculosis 
of  the  thyroid  is  rare.  Rokitansky,  in  1861,  denied  its  existence;  but  a 
few  years  later  Lebert  discovered  the  first  case,  and  lately  Arnd,  in 
looking  over  the  literature,  found  44  cases  which  seemed  to  be  undoubt- 
edly of  tuberculous  origin.  Of  course  tuberculous  foci  occurring  in 
miliary  tuberculosis  have  not  been  included  in  the  list,  as  they  are 
without  interest;  they  have  no  entity  per  se,  but  are  only  the  conse- 
quence of  a  generalized  process  extended  to  the  entire  organism. 

Follicular  tuberculosis  of  the  thyroid,  secondary  to  a  primary  focus 
localized  in  another  organ,  is  more  frequent  and  better  known.  Lebert, 
in  1862,  was  the  first  to  call  attention  to  it,  and  since  then  other  pathol- 
ogists have  studied  it.  Chiara  thinks  that  it  is  common  in  the  acute 
form  of  tuberculosis,  3  out  of  4  cases  (what  a  small  number  to  draw  con- 
clusions from),  but  rare  in  the  chronic  form,  4  out  of  96  cases.  Fraenkel 
and  some  other  authors  have  confirmed  these  results,  which  were,  how- 
ever, only  postmortem  findings. 

The  caseous  form  of  tuberculosis  of  the  thyroid  is  rare.  The  first 
case  was  published  by  Bruns  in  1893.  It  was  that  of  a  woman,  aged 
forty-one  years,  with  a  large  goiter  growing  rapid!)'  in  size.     The  tumor 


TUBERCULOSIS  OF   THE   THYROID  107 

was  hard,  painful  to  pressure,  had  diffuse  limits,  and  caused  shooting 
pains  and  dyspnea.  Bruns  considered  the  case  a  malignant  one,  but 
was  very  much  surprised  at  the  operation  to  find  only  a  caseous  tuber- 
culous goiter.  A  few  other  cases  have  been  reported  since,  and  in 
conclusion  it  may  be  said  that  caseous  tuberculosis  in  goiter  forms  a 
tumor,  more  or  less  hard  in  consistency,  painful  to  pressure,  with  dif- 
fuse limits  and  a  tendency  to  infiltrate  neighboring  tissues.  Diagnosis 
is  verv  seldom  made  before  the  operation. 

Localized  areas  of  tuberculosis  may  be  found,  too,  in  a  simple  goi- 
ter; no  clinical  or  pathological  symptoms  betray  their  presence,  and 
they  are  revealed  only  by  a  careful  microscopic  examination.  Ruppaner 
was  the  first  to  describe  such  a  condition,  and  reported  3  cases  of  col- 
loid goiter  in  which  he  was  able  to  detect  such  tuberculous  lesions.  \  on 
Werdt,  in  going  over  444  cases  of  simple  goiter,  found  similar  conditions 
three  times.  Out  of  29  exophthalmic  goiters  he  found  1  with  tuberculous 
areas. 

Arnd  found  3  cases,  Hedinger  10,  out  of  608  goiters.  The  tubercu- 
lous lesions  are  found  in  the  nodular  goiter  itself  or  in  the  normal  paren- 
chyma between  the  nodules.  Hedinger  thinks  that  tuberculous  lesions 
in  conjunction  with  goiters  are  more  frequent  than  is  thought,  because 
these  lesions,  being  so  little  apparent,  easily  escape  attention  unless 
looked  for  in  seriated  slides;  they  are  really  microscopic  findings. 

Besides  these  massive  as  well  as  tiny  tuberculous  lesions  a  more  or 
less  marked  sclerotic  condition  may  be  encountered  in  the  thyroid,  due  to  a 
chronic  toxic  irritation  from  the  tuberculous  toxins.  In  certain  instances 
sclerosis  may  become  so  developed  that  a  condition  of  canceriform 
appearance  known  as  woody  thyroiditis  follows;  the  tumor  is  hard  like 
wood,  has  diffuse  limits,  is  in  the  great  majority  of  cases  painful  to 
pressure,  and  rapidly  causes  marked  dyspneic  symptoms.  Its  true 
origin,  as  a  rule,  is  not  recognized  and  the  diagnosis  of  malignant  tumor 
is  nearly  always  made. 

Some  authors  seem  to  think  there  is  an  indisputable  relation  between 
goiter.  Basedow's  disease,  and  tuberculosis.  The  impression  gained 
from  the  small  amount  of  experimental  work  along  this  line  is  that  the 
thyroid  is  peculiarly  resistant  to  tuberculous  infections.  Pinoy,  injecting 
guinea-pigs  with  tuberculous  bacilli,  found  only  once  the  thyroid  gland 
infected  with  tuberculosis;  therefore  he  concluded  that  the  thyroid, 
as  well  as  the  pancreas  and  other  glands,  shows  a  special  resistance  to 
tuberculous  bacilli.  Torrin  and  Tomellini,  on  the  other  hand,  injecting 
directly  into  the  thyroid  artery  an  emulsion  of  tubercular  bacilli,  found 
in  each  case  the  corresponding  lobe  infiltrated  with  tuberculosis.  Shimo- 
daira  repeated  the  same  experiment,  but  in  one  series  injected  heavy 
doses  of  tubercle  bacilli  and  in  the  other  series  small  doses.     He  found 


108  INFLAMMATIONS  OF  THE  THYROID 

that  in  the  first  series  of  experiments  the  gland  was  infected  with 
tubercle  bacilli  while  in  the  other  it  was  not.  Therefore  he  concluded 
that  unless  overpowered  by  number  the  thyroid  gland  shows  a  special 
resistance  to  tubercle  bacilli. 

Many  seem  to  believe  that  the  thyroid  has  an  immunizing  influence 
against  tuberculosis,  not  only  for  the  gland  itself  but  also  for  the  entire 
organism.  Morin,  working  in  a  sanitarium  for  tuberculosis  in  Leysin, 
after  examining  several  hundred  tuberculous  patients,  came  to  the  con- 
clusion that  the  disease  undergoes  a  more  acute  and  malignant  course 
in  cases  in  which  the  thyroid  is  atrophied;  whereas  in  cases  in  which 
a  thyroid  hypertrophy  or  even  a  goiter  exists  the  course  of  the  disease 
is  milder.  I  do  not  know  how  far  these  conclusions  are  justified,  but 
it  is,  nevertheless,  a  fact  that  myxedematous  patients  are  easily  the 
prey  of  tuberculosis,  as  shown  by  McKenzie,  who  out  of  71  cases  of 
myxedema  found  that  20  were  tuberculous.  This,  however,  could  be 
explained  by  the  retarded  metabolism  and  the  diminished  resistance  of 
the  patients. 

Costa  goes  so  far  as  to  pretend  there  is  an  etiological  relation  between 
goiter  and  tuberculosis.  Goiter,  in  his  judgment,  is  due  to  the  reaction 
of  the  gland  against  tuberculous  toxins.  If  he  meant  that  the  thyroid 
may  react  to  tuberculous  toxins  by  toxic  thyroiditis,  all  well  and  good; 
otherwise  he  must  have  been  the  victim  of  coincidences,  because  we 
see  too  many  cases  of  goiter  in  which  no  tuberculous  lesions  are  found, 
and  vice  versa. 

Let  us  remember  that  Hedinger  found  10  microscopic  tuberculosis 
cases  out  of  608  cases.  Goiter  and  tuberculosis  are  among  the  most 
common  diseases,  and  if  there  were  any  etiological  relation  between 
the  two,  it  seems  that  this  fact  could  be  easily  demonstrated,  as  thou- 
sands of  cases  are  seen  each  year.  In  the  many  hundreds  of  cases  of 
goiter  which  I  have  seen,  pathologically  as  well  as  clinically,  tubercu- 
losis associated  with  goiter  was  only  an  accidental  occurrence. 

On  the  other  hand,  the  relation  of  cause  to  effect  between  Basedow's 
disease  and  tuberculosis  cannot  be  denied.  It  is  not  uncommon  to  find 
a  Graves'  disease  grafted  upon  a  case  of  early  tuberculosis;  even  marked 
exophthalmic  symptoms  may  develop  in  the  course  of  advanced  tuber- 
culosis. From  the  cases  I  have  seen,  however,  I  could  not  say  that 
tuberculosis  was  of  more  frequent  occurrence  in  the  history  of  my  Base- 
dow's patients  than  any  other  acute  illnesses,  as  typhoid,  pneumonia, 
tonsillitis,  etc.  I  shall  take  up  again  these  relations  between  acute 
infectious  diseases  and  Graves'  disease  in  the  chapter  on  the  Etiology 
of  Exophthalmic  Goiter. 

Syphilis  of  the  Thyroid. — It  is  only  recently  that  attention  has  been 
turned  to  syphilis  of  the  thyroid.     Only  very  few  cases  worth  any  ere- 


WOODY   THYROIDITIS  109 

dence  have  been  reported.  Demme,  according  to  \\61fler,  found  a 
syphilitic  gumma  in  the  thyroid  of  a  newborn.  In  1889  Gamier  described 
syphilitic  alterations  in  the  thyroids  of  five  newborn,  characterized  bv 
interstitial  sclerosis  and  alveolar  atrophy.  Lancereaux  found  about  the 
same  alterations.  Recently,  Poncet,  Leriche,  Berard,  Favre  and  Savy 
have  made  important  contributions  to  this  subject. 

Histologically,  lesions  of  the  thyroid  may  involve  the  interstitial  as 
well  as  the  parenchymatous  elements.  The  interstitial  connective  tis- 
sue has  a  marked  tendency  to  abnormal  proliferation,  spreads  through- 
out the  gland,  and  terminates  by  a  sclerosis  of  the  organ.  In  the  early 
stage,  epithelioid  nodules  and  giant  cells  are  frequently  seen  in  it. 
Diffuse  leukocyte  infiltration  is  the  rule. 

Woody  Thyroiditis. — It  was  Riedel  who,  in  1896,  first  described  a 
form  of  thyroiditis  which  he  called  "eisenharte  strumitis,"  or  "iron- 
hard  strumitis."  Riedel's  patient  was  a  man,  aged  forty-two  years, 
who  had  a  tumor,  developed  in  the  thyroid,  extremely  immobile  and 
causing  alarming  dyspneic  symptoms.  He  diagnosed  it  as  a  cancer  of 
the  thyroid  and  attempted  the  removal  of  the  tumor,  but  at  the  opera- 
tion the  difficulties  were  so  great,  the  adhesions  with  the  neighboring 
tissues  so  intense,  that  a  radical  operation  had  to  be  given  up.  He, 
however,  removed  a  piece  of  the  tumor  the  size  of  a  walnut  and  to  his 
great  surprise  after  a  few  months  the  patient  was  entirely  cured.  Micro- 
scopically, no  malignant  elements  were  found;  the  whole  thing  was 
simply  the  picture  of  a  chronic  inflammation.  On  account  of  the 
extremely  hard  consistency  of  the  tumor.  Riedel  called  it  "eisenharte 
strumitis."  In  the  same  year  Cordua,  of  Hamburg,  reported  a  similar 
case.  In  1898  Jeannel,  of  Toulouse,  reported  a  case  in  which  he  made  a 
diagnosis  of  cancer  of  the  thyroid;  later,  it  proved  to  be  a  case  of 
"eisenharte  strumitis."  In  1901  Ricard  reported  a  similar  case  in 
which  the  diagnosis  of  cancer  of  the  thyroid  had  been  made  and  which 
proved  to  be  a  case  of  "woody  thyroiditis."  Silatschek,  of  Innsbruck, 
and  Spannaus,  of  Breslau,  reported  lately  similar  cases. 

This  form  of  thyroiditis,  called  by  Riedel  "eisenharte  strumitis," 
or  "iron-hard  strumitis,"  and  by  Delore  and  Alamartine  "La  thyroidite 
ligneuse,"  "woody  thyroiditis,"  has  always  been  mistaken  for  a  malig- 
nant tumor,  and  yet  between  these  two  forms  of  disease  the  clinical 
differences  are  such  that  a  differential  diagnosis  can  often  be  made. 
First  of  all,  the  woody  thyroiditis  is  found  in  younger  people,  that 
is,  those  between  thirty  and  forty  years  of  age.  Men  are  more  often 
afflicted  with  it  than  women.  The  disease  evoluates  extremely  rapidly, 
in  a  few  weeks  or  months.  The  region  of  the  thyroid  is  painful  and 
shooting  pains  are  intense.  One  of  the  earliest  symptoms  is  dyspnea, 
which  may  become  so  rapidly  alarming  that  death  seems  imminent,  and 


110  INFLAMMATIONS  OF   THE  THYROID 

in  many  instances  tracheotomy  is  the  only  salvation.  The  dyspneic 
symptoms  are  due  to  the  fact  that  the  trachea  is  compressed  between 
the  lobes  of  the  inflamed  thyroid.  The  trachea  is  not  displaced  unless 
there  has  been  a  goiter  previously.  Pressure  symptoms  on  the  inferior 
laryngeal  nerve  show  up  early.  The  inflammation  extends  over  the 
entire  gland  and  seems  to  occur  more  frequently  in  normal  thyroids 
than  in  goiter.  Like  a  drop  of  oil,  it  spreads  and  infiltrates  all  the  organs 
found  between  the  superficial  and  prevertebral  fascia,  thus  forming  a 
gangue  in  which  everything  has  become  solidified :  thyroid,  trachea, 
esophagus,  neurovascular  cords,  sternocleidomastoid  muscles  and  muscles 
of  the  subhyoid  triangle  all  form  only  one  mass.  Vainly,  one  would 
try  to  find  in  it  a  plane  of  cleavage.  The  tumor  is  absolutely  hard  like 
iron  or  wood,  hence,  its  name.  Its  surface  is  smooth,  being  irregular 
only  when  a  goiter  existed  previously.  The  larynx,  immobilized  by  the 
diffuse  infiltration,  does  not  go  up  or  down  with  deglutition;  cervical 
lymphatic  glands  are  very  seldom  involved.  The  common  carotid  is 
lost  in  the  midst  of  the  infiltration,  whereas  in  a  cancer  of  the  thyroid, 
especially  if  there  has  been  a  previous  goiter,  it  is  displaced  backward. 

All  these  symptoms  taken  together  give  to  the  disease  a  physiog- 
nomy which  differs  from  the  one  of  malignant  tumors.  The  extreme 
hardness,  its  regularity  of  surface,  its  marked  diffuseness  of  limits,  the 
involvement  of  the  gland  in  toto  will  remind  one  more  of  woody  thy- 
roiditis than  of  a  cancer  of  the  thyroid,  especially  if  the  disease  is  found 
in  a  young  individual,  and  if  it  has  evoluated  rapidly  and  caused  early 
dyspneic  symptoms,  entirely  out  of  proportion  to  the  size  of  the  tumor. 

Pathologically,  the  gland  is  transformed  into  a  fibrous,  whitish, 
extremely  hard  mass.  If  a  goiter  has  existed  previously,  it  is  embedded 
in  the  fibrous  mass.  The  cut  surface  is  dry  and  no  juice  can  be 
expressed,  as  can  be  done  in  cancer.  Histologically,  the  parenchyma  is 
choked  by  a  sclerotic  connective  tissue  of  interstitial  and  capsular 
origin;  alveoli  in  places  have  disappeared;  there  is  no  abscess  nor  any 
tendency  to  suppuration.  In  the  remaining  alveoli,  desquamation  and 
either  thinning  or  absence  of  the  colloid  is  present. 

In  such  cases  the  idea  of  scirrhus  must  be  soon  discarded,  as  spon- 
taneous healing  has  been  observed,  and  a  complete  cure  without  relapse 
followed  partial  extirpation.  Fibromata  of  the  thyroid  have  not  the 
same  anatomical  and  clinical  aspect  either;  they  are  encapsulated  with- 
out tendency  to  infiltration. 

As  a  rule  the  disease  affects  individuals  who  have  been  in  excellent 
health  previously,  with  no  typhoid,  pneumonia,  or  other  infectious  dis- 
ease as  a  preliminary  stage.  In  some  instances,  it  is  true,  tuberculosis 
and  syphilis  have  been  found  as  a  concomitant  complication,  so  that  they 
might  be  considered  as  an  etiological  factor;  but  the  fact  remains  that 


PARASITIC  THYROIDITIS  111 

cases  of  woody  thyroiditis,  where  apparent  concomitant  infection  could 
be  discovered,  do  exist. 

This  fibrous,  sclerotic  process  is  not  peculiar  to  the  thyroid  only, 
but  had  also  been  found  by  Riedel  in  the  pancreas  and  by  Mickulicz 
and  Kuttner  in  the  submaxillary  and  lacrymal  glands.  The  same 
sclerotic  process  is  known,  too,  in  the  digestive  apparatus,  especially  in 
the  stomach  and  gall-bladder.  I  remember  finding  in  a  postmortem  a 
stomach  which  had  seemingly  undergone  the  same  kind  of  sclerotic 
degeneration  as  the  one  described  above  in  the  thyroid,  and  which  is 
known  as  the  "leather-bottle"  stomach.  The  stomach  was  transformed 
into  a  canal  about  40  cms.  in  length,  10  to  12  cms.  in  width  in  the  cardiac 
region,  and  6  to  8  cms.  in  the  pyloric  region.  This  canal  was  extremely 
hard,  its  walls  were  thick,  and  all  the  epigastric  region  was  diffusely 
involved  by  the  same  sclerotic  condition — no  metastases  of  any  kind; 
no  ulcerations  of  the  mucous  membrane  of  the  stomach.  Macroscopi- 
cally,  I  made  the  diagnosis  of  "limtis  plastica,"  which  was  considered  at 
the  time  as  a  peculiar  form  of  malignancy,  but  histologically  it  proved 
to  be  a  chronic  inflammation. 

Bacteriologically,  nothing  has  been  found  to  enlighten  us  on  this 
subject.  Mycosis,  and  especially  actinomycosis,  might  be  incriminated 
in  some  cases. 

In  view  of  the  extreme  diffuseness  of  the  lesions,  surgical  treatment 
which  intends  to  be  radical  is  extremely  dangerous,  as  extirpation  can- 
not be  complete  without  sacrificing  important  organs  as  the  common 
carotids,  vagus  nerve,  and  the  jugular  veins.  On  the  other  hand,  infiltra- 
tion of  the  walls  of  these  vessels  makes  the  attempt  dangerous  as  they 
are  very  friable;  ligatures  cut  through  as  if  in  butter.  If  the  dyspneic 
symptoms  become  so  alarming  as  to  endanger  the  life  ot  the  patient,  the 
best  treatment  is  a  cuneiform  resection  of  the  isthmus  in  order  to  liberate 
the  trachea  from  its  compressing  ring.  If  an  operation  is  decided  upon, 
then,  according  to  Delore  and  Alamartine,  an  excision  of  a  small  portion 
of  the  tumor  seems  to  be  sufficient  to  assure  complete  recovery.  Iodide 
of  potash  is  an  excellent  adjuvant,  and  x-ray  treatment  seems  to  be, 
according  to  Silatschek  and  Barjon,  specific  for  this  disease.  If  syphilis 
is  suspected,  an  intense  antisyphilitic  treatment  should  be  started  at 
once. 

Parasitic  Thyroiditis. — In  1907  Chagas,  working  in  the  Institute  of 
Manghuinos  in  Rio  de  Janeiro,  discovered  a  new  parasite  which  he 
called  "  Schizotrvpanum  cruzi"  in  honor  of  his  chief,  Oswald  Cruz. 
According  to  Chagas  this  living  organism  causes  a  parasitic  thyroid- 
itis, accompanied  by  the  most  severe  symptoms,  and  is  very  often  fatal. 
The  geographical  distribution  of  this  disease  is  not  entirely  worked 
out.     It  is  found  in  Brazil,  especially  in  the  State  of  Minas  Geraes.     It 


112  INFLAMMATIONS  OF   THE  THYROID 

is  transmitted  to  human  beings  and  to  domestic  animals  by  the  bite 
of  a  hematophagus  insect,  the  "  Conorrhinus  megistus."  This  hemip- 
terus  lives  in  the  cracks  of  windows  and  walls  of  old  huts;  it  is  not 
found  in  new  houses,  consequently  the  disease  is  mostly  found  among 
the  poorer  class  of  people. 

The  insect  bites  during  sleep.  Its  bite  is  absolutely  painless  and 
does  not  cause  any  inflammatory  reaction.  It  is  not  uncommon  to  see 
a  dozen  or  more  of  these  insects  biting  at  the  same  time  a  sleeping 
infant  without  waking  it.  The  parasite  is  found  in  the  blood  under 
different  forms,  according  to  the  stage  of  its  evolution.  It  can  be  culti- 
vated on  blood  agar.  The  period  of  incubation  after  its  bite  is  about 
ten  days.  According  to  Brumpt,  other  insects  can  also  act  as  hosts, 
especially  the  bed-bug  (Cimex  lectulanus),  the  excreta  of  which  are 
highly  infectious. 

Parasitic  thyroiditis  may  be  acute  or  chronic.  The  acute  form  is 
found  mostly  in  children  under  one  year  of  age.  The  thyroid  is  swollen, 
skin  is  infiltrated  not  only  in  the  neck  but  over  the  face,  and  a  crepitus 
on  pressure  is  present.  Fever  is  persistent,  high,  1030,  with  only  slight 
morning  remissions.  Cervical  glands,  spleen,  and  liver  are  enlarged. 
The  disease  lasts  about  fifteen  to  thirty  days,  and  terminates,  as  a  rule, 
in  death.  Only  exceptionally  does  it  take  a  chronic  course  in  very 
young  children. 

The  chronic  form  is  found  in  older  and  more  resistant  children  and 
in  adults.  If  the  disease  does  not  terminate  fatally,  it  lapses  into  a  chronic 
form  characterized  by  goiter,  often  of  very  large  size,  and  symptoms 
due  to  partial  or  total  loss  of  the  thyroid  function  dominate  the  scene. 
According  to  the  degree  of  thyroid  disturbance  the  symptoms  may  be 
slight,  moderate,  or  very  pronounced.  It  is  possible,  therefore,  to  meet 
with  cases  which  are  practically  indistinguishable  from  the  usual  type 
of  goiterous  individuals  seen  in  endemic  localities  in  Europe.  It  is 
impossible  to  distinguish  such  cases  from  the  true  endemic  goiter  by 
blood  examination,  since  the  trypanosoma,  which  is  said  to  cause  the 
goiter,  disappears  from  the  blood  after  the  acute  symptoms  have  sub- 
sided; the  true  infectious  origin  of  this  goiter  can  be  ascertained  by 
inoculation  methods. 

Chagas  described  five  different  forms  which  the  disease  may  take: 

1.  The  pseudomyxedematous  form:  the  thyroid  is  enlarged,  the 
enlargement  being  confined,  as  a  rule,  to  one  lobe  only;  the  skin  shows  a 
mucoid  infiltration  and  has  a  bronze  color,  similar  to  the  color  charac- 
teristic of  Addison's  disease;  irregular  and  intermittent  fever  is  present. 

2.  The  myxedematous  form:  symptoms  of  hypothyroidism  are 
extremely  marked. 

3.  The  cardiac  form:  found  mostly  in  adults  and  characterized  by 
myocarditis,  arrhythmia,  and  bradycardia. 


HYDATID  CYST  OF  THE  THYROID  113 

4.  The  nervous  form:  caused  by  the  localization  of  parasites  in  the 
central  nervous  system;  spasmodic  motorv  disturbances  are  frequently 
seen  in  that  form. 

5.  The  subacute  form:  characterized  by  periods  of  exacerbation 
alternating  with  periods  of  remission;  the  prognosis  of  this  form  is 
severe. 

Postmortem  shows  enlargement  of  the  thyroid  and  of  the  cervical 
glands;  cardiac  hypertrophy  with  a  pericardiac,  pleuritic,  peritonitic, 
serous  exudate  is  frequent.  Liver,  spleen,  and  suprarenal  bodies  are 
enlarged.  Histologically,  what  dominates  in  both  forms,  acute  and 
chronic,  is  sclerosis  due  to  an  exaggerated  development  of  connective 
tissue.  The  alveoli  are  choked  and  atrophied.  In  the  acute  forms, 
proliferation  and  desquamation  of  the  epithelium,  thinning  or  absence 
of  the  colloid,  hyperemia,  leukocyte  infiltration,  in  short,  the  same 
lesions  found  in  all  the  other  forms  of  acute  thyroiditis  are  present.  In 
chronic  cases  the  connective  tissue  is  very  abundant  and  cystic  forma- 
tions of  more  or  less  large  size  are  found  in  great  numbers.  The  same 
inflammatory  reactions  and  cystic  formations  can  be  found  in  the  myo- 
cardium, muscles,  nerves,  testicles,  ovaries,  cortex  cerebri,  etc. 

In  the  acute  form,  as  the  parasites  are  numerous,  a  simple  drop  of 
blood  taken  from  the  finger  or  lobule  of  the  ear  will  show  the  parasite 
when  colored  by  the  Giemsa  method.  In  the  chronic  forms  5  to  10  c.c. 
of  blood  injected  into  the  vein  of  a  dog,  monkey,  or  cat  will  kill  the 
animal  after  a  certain  period  of  time:  the  schizogonic  form  of  the  parasite 
will  then  be  found  in  the  lungs. 

Most  significant  analogies  between  what  Chagas  calls  the  endemic 
Brazilian  goiter  in  its  chronic  form  and  our  own  endemic  goiter  cannot 
be  denied.  In  both  cases  there  exists  the  chronic  enlargement  of  the 
thyroid  gland  with  its  accompanying  conditions  of  cretinism  and  myx- 
edema. Beyond  doubt  the  Brazilian  infection  is  much  more  severe  and 
the  mode  of  infection  and  infectious  agent  totally  different,  but  these 
conditions  do  not  change  the  fact  that  a  chronic  goiter  is  developed 
from  an  infectious  basis.  This  is,  in  my  judgment,  a  very  strong  argu- 
ment in  favor  of  the  infection  theory  of  our  endemic  goiter. 

Hydatid  Cyst  of  the  Thyroid. —  Hydatid  cysts  of  the  thyroid  are 
extremely  rare.  L.  A.  Landiver  went  over  the  literature  and  found  29 
cases,  to  which  he  adds  2  of  his  own.  The  hexacantic  infection  takes 
place  through  the  hematogenous  route.  Direct  inoculation  occurs  only 
in  a  very  extraordinary  condition,  as  in  Minert's  case — there  the  cervical 
wound  was  licked  by  a  dog. 

The  pathological  characters  of  the  hydatid  cyst  do  not  differ  from 
those  of  a  simple  cyst.  The  parenchyma  undergoes  sclerosis  on  account 
of  compression.     If  the  hydatic  cyst  becomes  infected,  we  have  then  the 


114  INFLAMMATIONS  OF  THE  THYROID 

symptoms   of  a   cystic  strumitis.      Clinically,  the  diagnosis  of  hydatid 
cyst  is  seldom  made,  as  the  only  symptom  pathognomonic  of  its  pres- 
ence, namely,  the  "hydatid  fremitus,"  has  never  been  perceived. 
Treatment,  of  course,  must  be  surgical. 


CONGESTIONS    OF    THE    THYROID. 

Possibly  more  than  any  other  organ  the  thyroid  is  exposed  to  conges- 
tions of  various  origin,  physiological  or  pathological.  These  congestions 
have  a  great  clinical  importance. 

Physiological  congestions  are  observed  most  frequently  in  women 
and  especially  during  their  genital  life.  Premenstrual  congestion  of  the 
thyroid  is  among  the  most  frequent  premonitory  symptoms  of  the  first 
menstruation.  Mothers  often  worry  over  this  "physiological  goiter." 
Not  all  have  the  wisdom  of  the  one  mentioned  by  Goethe,  who  said  to 
her  daughter:  "Do  not  worry,  my  child,  Venus  has  touched  thee  with  her 
enchanted  hand." 

Of  course,  in  such  conditions  congestion  is  accompanied  with  true 
glandular  hypertrophy.  When  once  the  menstruation  is  well  estab- 
lished, congestion  of  the  thyroid  may  subside  more  or  less  entirely. 
In  many  cases,  however,  it  reappears  each  month  with  the  menstrual 
period,  and  in  dysmenorrheic  patients  it  may,  indeed,  be  very  marked,  as 
if  the  thyroid  were  trying  to  exert  a  vicarious  function. 

That  congestion  in  the  thyroid  takes  place  during  the  first  sexual 
relations  is  a  fact  known  since  antiquity.  It  was  a  popular  custom 
among  the  old  Roman  matrons  to  measure  the  circumference  of  the  neck 
before  and  after  marriage,  and,  as  Berard  says,  "More  than  one  Roman 
husband  measured  the  virginity  of  his  wife  by  the  length  of  the  thread 
rolled  around  her  neck." 

Later  on,  during  pregnancies  and  especially  during  delivery,  the 
thyroid  is  again  the  site  of  congestion.  This  increase  in  volume  is 
partly  due,  of  course,  to  hypertrophy  of  the  glandular  elements,  but 
active  and  passive  congestions  play  a  very  important  part  in  it  also. 
After  delivery,  hypertrophy  and  congestion  retrocede  gradually,  but, 
as  a  rule,  the  volume  of  the  thyroid  never  goes  back  to  its  normal  size. 

At  the  menopause  there  is  again  occasion  for  congestions  of  the  thy- 
roid; they  are  the  last  "flaring  up"  of  the  genital  process,  which  is 
going  to  be  set  at  rest  forever.  Too  often,  however,  these  congestions 
of  the  menopause  are  of  bad  augur,  as  they  are  the  premonitory  symptoms 
of  a  malignant  goiter. 

In  young  boys  these  same  transitory  congestions  are  seen  at  the 
time  of  puberty. 


TRAUMATIC  LESIOXS  OF   THE  THYROID  115 

Congestion  following  physical  effort  is  a  well-known  fact,  and  is  of 
frequent  occurrence.  Already  Lalouette  and  Maigmen  were  aware  of 
that  fact.  They  demonstrated  experimentally  that  in  dogs,  after  a 
prolonged  and  fatiguing  run,  the  thyroid  became  a  third  larger.  This 
increase  in  size  was  due  to  venous  congestion.  These  congestions  due 
to  physical  effort  are  seen  in  all  walks  of  life — singers,  officers,  workmen 
lifting  heavy  weights  are  especially  liable. 

Congestions  in  congenital  goiter  will  be  taken  up  in  the  chapter 
reserved  for  that  subject. 

Pathological  Anatomy. — \  erv  little  was  known  of  the  congestive 
lesions  in  man  until  De  Quervain,  Berard,  Ball  and  others  approached 
this  question  experimentally.  What  strikes  the  attention  at  first  is  a 
marked  dilatation  of  the  vessels  of  the  capsule,  which  are  abnormally 
distended  and  filled  with  black  blood.  On  the  cut  surface  the  alveoli 
and  capsular  vessels  are  dilated  and  bulge  out.  Microscopically,  beside 
the  intense  vascularization  and  the  interstitial  hemorrhages,  what  im- 
presses one  is  the  fact  that  the  alveoli  contain  no  colloid  or  very  little, 
whereas  the  intra-  and  perilobular  lymphatics  contain  a  great  quantity 
of  it.  At  the  same  time  a  more  or  less  intense  desquamation  of  the 
epithelium  is  present. 

Symptoms. — As  a  rule  the  only  symptom  seen  in  congestion  of  the 
thyroid  is  a  swelling  of  the  thyroid.  Palpation  shows  an  enlarged  gland, 
soft  or  firm,  and  slightly  painful  to  pressure.  It  is  only  when  a  goiter 
of  quite  large  size  is  present  that  the  congestions  of  the  thyroid  are 
liable  to  cause  dyspneic  symptoms. 

The  prognosis  of  such  conditions  is  extremely  benign.  After  a  few 
days  or  weeks  the  congestive  symptoms  retrocede  and  the  gland  is 
restored  to  normal  condition.  In  the  newborn  the  prognosis  is  not 
always  so  simple,  as  we  shall  see  in  the  chapter  on  Congenital  Goiter. 

Treatment.  In  the  great  majority  of  cases  expectation  is  the  only 
reasonable  treatment.  If  during  pregnancy  the  dyspneic  symptoms 
become  so  marked  as  to  endanger  the  life  of  the  patient,  thyroidectomy, 
Cesarean  section,  or  an  abortion  may  be  given  serious  consideration. 
The  nature  of  the  intervention,  of  course,  will  depend  upon  the  case. 

TRAUMATIC    LESIONS    OF    THE    THYROID. 

On  account  of  its  natural  vertical  as  well  as  lateral  mobility,  and 
on  account  of  the  protection  afforded  to  it  by  the  muscles  of  the 
cervical  region,  the  thyroid  gland  is  seldom  involved  in  traumatisms  ot 
rlu-  cervical  region;  however,  injuries  of  that  gland  may  occur  and  may 
be  of  such  importance  as  to  endanger  the  life  of  tin-  patient  and  to  call 
for  immediate  surgical  help. 


116  INFLAMMATIONS  OF  THE  THYROID 

Contusions. — When  a  goiter  more  or  less  large  in  size  is  present,  the 
traumatism  does  not  need  to  be  a  great  one  in  order  to  determine  intra- 
parenchymatous  or  intracystic  hemorrhages.  When  this  occurs,  the 
increase  in  volume  is  sudden  and  may  cause  marked  dyspnea.  But 
when  the  thyroid  is  normal,  the  traumatism  must  be  a  severe  one  to 
determine  lesions  in  the  thyroid.  This  occurs  mostly  in  strangulation, 
hanging,  and  other  severe  accidents  bearing  directly  upon  the  thyroid. 
The  consequences  of  such  injuries  to  the  gland  are  multiple;  the  most 
important  are  the  intra-  and  periglandular  ecchymosis  and  hemorrhages. 

The  concomitant  disturbances  in  respiration,  phonation,  and  degluti- 
tion are  nearly  always  due  to  fractures  of  the  laryngotracheal  carti- 
lages. Thyroiditis  may  be  the  consequence  of  such  contusions;  even 
development  of  myxedema  has  been  reported  by  Guerlain-Dudon  as  the 
result  of  a  direct  traumatism  of  the  thyroid  by  the  wheel  of  a  wagon. 
Most  likely  in  that  case  the  gland  underwent  connective-tissue 
degeneration. 

Wounds. — At  the  time  when  thyroid  surgery  was  not  so  far  advanced, 
modifying  as  well  as  aspirating  punctures  were  in  great  vogue.  Some- 
times they  gave  rise  to  very  troublesome  accidents.  Aspirating  punc- 
tures of  an  abscess  or  cyst  often  determined  hemorrhages  a  vacuo;  injec- 
tions of  modifying  substances,  as  tincture  of  10dm  for  instance,  were 
always  most  dangerous,  and  quite  a  number  of  sudden  deaths  have 
been  reported  after  the  use  of  such  punctures.  Today  these  thera- 
peutic measures  have  been  almost  entirely  discarded. 

Wounds  caused  by  sharp  instruments  are  more  serious.  They  occur, 
as  a  rule,  in  attempts  to  commit  suicide,  and  are  mostly  situated  in 
the  upper  portion  of  the  lobe  near  the  vascular  pedicle,  thus  causing 
profuse  hemorrhage.  Such  wounds,  of  course,  are  accompanied  by 
injuries  of  the  superficial  veins,  of  the  vessels  of  the  capsule,  and  in  some 
instances  of  the  vascular  cord;  even  the  laryngotracheal  canal  may  have 
been  opened.  In  all  these  traumatisms  the  hemorrhage  is  profuse,  and 
death  occurs  if  surgical  help  is  not  brought  in  time. 

Before  the  antiseptic  period,  wounds  inflicted  with  fire-arms,  because 
of  hemorrhage  and  suppuration,  were  more  dangerous  than  they  are 
today.  This,  however,  was  not  always  the  case.  At  the  battle  of 
Cerisoles,  commanded  by  the  Duke  d'Enghien,  under  Francois  I,  the 
young  Swiss,  Philip  von  Hohendax,  who  despite  his  youth  had  quite  a 
large  goiter,  was  struck  in  the  neck  with  a  large  pick.  The  goiter, 
fortunately,  was  a  large  cyst,  so  that  the  accident  proved  a  lucky  one, 
as  it  cured  the  patient  of  his  goiter.  Wounds  by  our  modern  rifles  with 
their  small,  thin  bullets  have  proved  more  than  once  to  be  benign  unless 
such  injuries  are  accompanied  by  severe  injury  of  other  organs.  On 
account  of  its  speed  and  small  size  the  bullet  goes  easily  through  the 


TRAUMATIC  LESIOXS  OF  THE  THYROID  117 

thyroid,  making  only  a  very  small  hole,  and  unless  a  vessel  of  impor- 
tance is  struck  at  the  same  time  the  hemorrhage  is  not  of  great  conse- 
quence, and  is  stopped  automatically  by  the  glandular  debris  formed 
by  the  passage  of  the  bullet.  Infections  of  such  wounds  are  very  uncom- 
mon. During  the  late  war  between  Japan  and  Russia  many  of  such 
cases  were  observed,  but  frequently  no  ill  effects  followed. 

Treatment. — If  surgical  interference  is  thought  necessary,  the  first 
indication  is  to  widen  the  wound  by  a  large  incision,  in  order  to  be  able 
to  get  a  better  view  of  the  deep  tissues. 

The  second,  to  put  hemostats  on  all  the  bleeding  vessels  and  ligate 
them. 

The  third,  to  clean  out  thoroughly  the  surgical  field  if  it  is  necessary. 

The  fourth,  to  sew  up  the  injured  gland  either  by  continuous  or 
interrupted  sutures. 

The  fifth,  only  in  very  rare  instances,  when  a  lobe  has  been  smashed 
into  pieces,  the  resection  of  that  lobe  is  to  be  given  serious  consideration. 

The  sixth,  to  leave  a  small  drain  for  twenty-four  to  forty-eight  hours 
or  longer  if  necessary. 

The  seventh,  to  sew  up  the  skin. 


CHAPTER  VI. 

ANATOMICO-PATHOLOGICAL  RELATIONS  OF  GOITER  TO 
THE  SURROUNDING  STRUCTURES. 

Structures  with  which  a  goiter  may  come  in  contact  are: 
i.   Sternocleidomastoid,   sternohyoid,    sternothyroid,    and    omohyoid 
muscles  with  their  cervical  fasciae. 

2.  Larynx  and  trachea. 

3.  Pharynx  and  esophagus. 

4.  Bloodvessels,  common  carotid,  superior  and  inferior  thyroid 
arteries,  internal  jugular  vein;  in  intrathoracic  goiter  both  innominates, 
the  arch  of  the  aorta  and  basis  of  the  heart  may  come  in  contact  with 
the  tumor. 

5.  Nerves:  vagus  with  its  superior  and  inferior  laryngeal  branches; 
sympathetic. 

6.  Sternum,  clavicles  and  superior  opening  of  the  thorax. 

7.  While  extending  upward  a  goiter  may  come  in  contact  with  the 
hyoid  bone,  the  digastric,  hyoglossus  and  mylohyoid  muscles,  the 
submaxillary  gland,  and  the  hypoglossus  nerve. 

8.  While  developing  laterally,  a  goiter  may  fill  the  posterior  triangle 
of  the  neck,  compress  the  spinal  accessory  nerve  and  go  as  far  as  the 
anterior  border  of  the  trapezius  muscle. 

9.  Owing  to  the  fact  that  the  thyroid  gland  lies  on  a  hard  surface, 
formed  by  the  transverse  processes  of  the  cervical  vertebrae,  covered  by 
the  deep  muscles  of  the  neck,  a  growing  goiter  most  naturally  develops 
forward,  laterally,  and  downward;  its  upward  extension  is  less  fre- 
quent, and  is  found  mostly  in  certain  large  parenchymatous  goiters, 
and  in  those  developed  in  the  upper  poles  or  in  the  pyramidal  process. 

10.  The  relations  of  a  goiter  to  the  surrounding  structures  will 
differ  notably  if  we  have  to  deal  with  a  diffuse  parenchymatous  goiter  or 
a  nodular  one. 

11.  A  diffuse  parenchymatous  goiter,  unless  of  unusual  dimensions, 
occupies  the  position  of  the  normal  gland,  and  consequently  has  no 
material  influence  on  the  surrounding  structures.  On  the  whole,  it 
retains  the  shape  of  the  normal  gland.  Only  in  very  voluminous  goiters 
do  we  see  the  upper  poles  extend  upward  as  far  sometimes  as  the  angle 
of  the  jaw  and  then  come  in  contact  with  the  thyroid  cartilage,  the 
hyoid  bone,  the  mylohyoid  and  digastric  muscles,  and  the  hypoglossus 


PLATE    VI 


.ikf1^ 


Cross-section  of  the  Neck  Showing  the    Relation  of  a  Goiter  to  the 

Surrounding  Structures. 


RELATIOX  OF  GOITER   TO  SKIX  AXD  MUSCLES  119 

nerves.  In  its  downward  growth  the  goiter  grows  alongside  and  in 
front  of  the  trachea  and  esophagus,  in  front  of  the  carotid  sheath  and 
of  the  vagus  and  sympathetic  nerves.  Anteriorly,  the  two  hyperplastic 
lobes  and  isthmus  cover  a  more  or  less  great  portion  of  the  trachea,  of 
the  cricoid  and  thyroid  cartilages.  The  processus  pyramidahs  partici- 
pates, as  a  rule,  only  in  a  moderate  degree  in  the  hyperplasia.  Laterally 
and  in  front  the  goiter  is  covered  by  the  muscles  of  the  cervical 
region. 

If  hyperplasia  is  more  or  less  evenly  distributed  over  the  whole  of 
the  thyroid,  there  is  practically  no  displacement  of  the  trachea  and  esoph- 
agus; displacement  of  the  latter  organs  takes  place  only  when  one  lobe 
of  the  gland  is  larger  than  the  other  one.  However,  displacement  or 
compression  of  the  windpipe  is  seldom  severe  with  diffuse  parenchy- 
matous goiters.  In  that  type  of  goiter  we  do  not  find  the  intense  dyspnea 
and  the  same  intensity  of  choking  spells  that  we  encounter  in  nodular 
goiter.  If,  however,  the  hyperplastic  goiter  grows  around  the  trachea 
and  esophagus  so  as  to  form  a  "circular  goiter,"  then  dyspnea  and 
dysphagia  may  be  quite  marked. 

Because  diffuse  parenchymatous  goiter,  especially  when  it  has 
reached  large  dimensions,  compresses  the  large  vascular  trunks  on  both 
sides,  and  because,  too,  such  goiters  more  than  any  others,  except  the 
thyrotoxic,  are  subjected  to  congestions,  impairment  of  the  venous  circu- 
lation of  the  neck  is  not  uncommonly  seen.  It  does  not,  however,  reach 
the  same  degree  of  intensity  as  in  intrathoracic  goiters. 

Nerves  are  very  rarely  injured  by  the  diffuse  parenchymatous  goiter; 
the  inferior  laryngeal  nerve,  however,  may  show  some  symptoms  of 
compression. 

Not  infrequently  does  the  diffuse  parenchymatous  goiter  extend 
downward  behind  the  sternum.  When  it  does,  it  is  only  in  a  moderate 
degree,  and  especially  in  cases  where  the  thyroid  is  situated  abnormally 
low  (thyroptosis  of  Kocher). 

Entirely  different  are  the  relations  of  the  nodular  goiter  to  the  sur- 
rounding structures.  Of  course  here,  again,  such  relations  are  deter- 
mined by  the  size  of  the  goiter.     (Plate  VI.) 

Relation  of  Goiter  to  Skin  and  Muscles  (Plate  VI). — In  certain 
forms  of  goiter,  especially  in  pendulous  goiter,  the  skin  may  become  so 
distended  and  elongated  as  to  form  a  real  pedicle. 

At  first,  during  the  slow  but  progressive  growth  of  the  goiter,  the 
cervical  muscles  covering  the  goiter  undergo  a  certain  amount  of  hyper- 
trophy, thus  forming  a  powerful  muscular  belt  whose  spasmodic  con- 
traction during  choking  spells  can  but  increase  their  intensity.  I  his  is 
proved  by  the  fact  that  the  transverse  section  of  this  muscular  belt 
relieves  dyspnea   very  materially.     Later,   however,  when   the  nodular 


120  ANATOMICO-PATHOLOGICAL  RELATIONS  OF  GOITER 

goiter  has  reached  voluminous  dimensions  on  account  of  prolonged 
pressure  and  displacement  the  muscles  finally  undergo  atrophy  and 
degeneration;  the  muscular  fibers  become  thin,  pale,  friable,  dissociated, 
sometimes  hardly  recognizable.  The  sternocleidomastoid  muscles,  too, 
participate  in  this  atrophy,  although  in  a  lesser  degree. 

Relation  of  Goiter  to  the  Larynx  and  Trachea  ( Plate  VI). — Already  in 
1817  Aepli,  then  Soemmering  in  1820,  and  others  called  attention  to  the 
various  forms  of  deformation  of  the  trachea  most  frequently  seen  in 
connection  with  goiter.  In  1861  Demme  gave  a  magistral  description 
of  the  pathological  trachea  in  goiter  and  insisted  especially  on  the 
"sabre-sheathed"  trachea  (Fig.  27).  These  deformations  were  thought 
to  be  of  purely  mechanical  order.  In  1878,  however,  Rose,  although 
admitting  that  the  etiology  of  tracheal  deformations  was  partly  mechan- 
ical, insisted  that  a  great  number  of  sudden  deaths  seen  in  such  condi- 
tions was  due  to  the  sudden  collapse  of  the  walls  of  the  windpipe  on 
account  of  their  degeneration  and  atrophy.  The  microscope  showed  that 
not  only  congestive  lesions  of  the  mucous  membrane  were  present,  but 
that  also  a  marked  fatty  degeneration  of  the  cartilaginous  rings  of  the 
trachea  and  of  the  elastic  and  muscular  fibers  of  the  posterior  membrane 
had  occurred.  Demme,  Eppinger,  Berard  and  others  have  more  or  less 
confirmed  these  findings.  Indeed,  it  seems  logical  to  admit  that  an 
organ  which  is  constantly  undergoing  pressure  is  bound  to  undergo 
atrophy  and  degeneration  in  the  course  of  time.  At  any  rate,  one  who 
has  seen  goiters  knows  that  the  "ribbon-shaped"  trachea  is  not  rare,  and 
that  mechanical  and  secondary  alterations  intervene  to  form  such  a 
trachea. 

Tracheal  deformations  in  nodular  goiters  are  found  in  about  50  per 
cent,  of  the  cases.  This  has  been  confirmed  by  O.  Wild  with  trache- 
oscopy, and  PfeifFer  with  radiography. 

The  effects  of  pressure  on  the  windpipe  are  manifold: 

1.  If  the  nodular  goiter  develops  in  one  lobe,  the  other  one  being 
more  or  less  normal,  the  trachea  assumes  a  curved  direction  with  the 
convexity  toward  the  sound  side  (Fig.  26).  At  the  same  time  the  trachea 
and  larynx  rotate  around  their  long  anterior  axis  because  the  latter 
one  is  held  more  or  less  firmly  by  the  thyroid  suspensory  ligament  and 
the  hyoid  bone,  whereas  the  posterior  border  is  free  from  such  attach- 
ment; it  rotates  along  the  anterior  border  and  in  the  opposite  direction 
of  pressure. 

2.  If  a  nodular  goiter  is  developed  in  each  lobe,  and  if  these  two  goi- 
ters are  more  or  less  of  the  same  level,  the  trachea  may  be  so  compressed 
on  each  of  its  sides  that  the  walls  of  the  trachea  may  come  in  contact 
one  with  the  other  and  form  what  we  call  the  sabre-sheathed  trachea 
(Fig.  27).     This  form  of  deformation  of  the  trachea,  although  possibly 


RELATION  OF  GOITER  TO  LARYXX  AXD  TRACHEA 


121 


less  frequent  than  the  former,  is  infinitely  more  dangerous,  and  is  the 
one  which  may  prove  fatal.  This  is  easily  explained.  Although  as  the 
result  of  pressure  the  walls  of  the  trachea  may  have  undergone  consid- 
erable atrophy,  as  long  as  the  trachea  remains  in  intimate  connection 
with  the  goiter,  the  latter  playing  the  role  of  a  splint,  there  is  no  chance 
for  the  tracheal  walls  to  be  sucked  in  during  inspiration.  But  let  us 
remove  the  goiter,  then  atrophied,  degenerated,  and  having  lost  their 
normal  resistance  and  elasticity,  the  walls  of  the  trachea  are  unable  to 
withstand  successfully  the  changes  of  air-pressure  in  the  bronchial  tube; 


Fig.  26. — Unilateral   compression   of 
the  trachea  by  a  nodular  goiter. 


Fig.  27. — Bilateral  compression  of  the 
trachea  taking  place  at  the  same  level. 
Sabre-sheathed  trachea. 


they  float  in  and  out;  expand  during  expiration  and  collapse  during 
inspiration:  hence  suffocation.  The  more  laborious  the  inspiration  is, 
the  tighter  is  the  suction.  Every  surgeon  has  probabl}  more  than  once 
experienced  such  a  tracheal  collapse  during  operation.  At  any  rati. 
everyone  who  does  thyroid  surgery  should  be  acquainted  with  such  an 
eventuality,  and  should  know  how  to  guard  his  patient  against  it. 

3.  If  two  nodular  goiters  develop  in  each  lobe,  but  at  different 
levels,  then  the  trachea  assumes  an  S-shape  analogous  to  the  scoliosis  ol 
the  spinal  column  (Fig.  _v 


122 


ANATOMICO-PATHOLOGICAL  RELATIONS  OF  GOITER 


4.  If  a  goiter  develops  in  the  isthmus,  its  size  does  not  need  to  be 
very  large  to  produce  symptoms  of  pressure.  As  the  isthmus  is  firmly 
attached  to  the  cricoid  cartilage  by  the  thyroid  suspensory  ligament  a 
goiter  developed  in  the  isthmus  will  naturally  not  be  able  to  wander 
far  even  if  it  attains  a  large  volume;  it  is  kept  in  front  of  the  windpipe, 

where  compression  takes  place 
anteropostenorly,  which  fact  is  soon 
betrayed  by  marked  dyspneic  symp- 
toms (Fig.  29).  In  such  conditions 
the  large  diameter  of  the  tracheal 
lumen  is  frontal,  whereas  in  the 
sabre-sheathed  trachea  it  is  sagittal. 
Such  a  goiter  is  called  struma  mediana 
or  median  goiter.  In  its  further 
development  the  median  goiter  may 


Fig.  28. — Bilateral  compression  of 
the  trachea  taking  place  at  two  differ- 
ent levels,  thus  forming  the  S-shaped 
trachea. 


Fig.  29. — Pressure  on  the  trachea  and  esoph- 
agus taking  place  anteroposteriorly. 


gradually  sink  downward  and  become  intrathoracic.  This  goiter  rarely 
develops  in  the  isthmus  alone;  as  a  rule  it  develops  at  the  junction  of 
the  lobe  with  the  isthmus. 

5.  A  goiter  developed  in  the  processus  pyramidalis  is  a  rare  feature. 
It  is  situated  in  the  middle  line  or  a  little  outside  of  it,  high  up  in  front 
of  the  larynx,  and  is  quite  superficial.  Let  us  call  this  form  of  goiter 
pyramidal  goiter  (Fig.  30). 

6.  In  certain  cases,  especially  in  newborn,  each  lobe  of  the  thyroid 
may  extend  behind  the  trachea  and  esophagus  to  such  an  extent  as  to 
come  into  contact  one  with  another;  trachea  and  esophagus  are  then 
surrounded  with  a  ring  of  glandular  tissue.  That  is  the  circular  goiter 
(Fig.  50).     We  shall  study  it  in  a  chapter  by  itself. 

Besides  the  trachea  the  larynx  may,  too,  be  compressed  and  dis- 
placed by  a  large  goiter.     Such  modifications  of  positions  of  the   larynx 


RELATION  OF  GOITER   TO  PHARYNX  AND  ESOPHAGUS       123 

and  changes  of  consistency  of  its  cartilages  are  apt  to  cause  phonetic 
disturbances,  due  only  to  a  rupture  of  the  anatomical,  statical,  and 
muscular  equilibrium;  the  vocal  cords  may  be  normal  but  the  points 
of  insertion  are  slightly  displaced;  hence  a  slightly  disturbed  synergical 
action  of  both  cords. 

As  can  be  easily  foreseen,  all  these  pathological  modifications  of  the 
laryngotracheal  tube  give  rise  to  congestion  of  its  mucous  membrane,  and 
as  these  irritations  are  eminently  chronic,  the  mucous  membrane  becomes 
edematous,  thickened,  and  congested.  The  clinical  importance  of  these 
lesions  cannot  be  ignored.     Take,  for  instance,  cases  in  which  tracheo- 


FlG.   }o. —  (inner  developed  in  the  pyramidal  process. 


stenosis  is  so  developed  that  the  patient  has  barely  enough  lumen  left 
for  respiration.  Suppose  now  that  for  some  reason  an  active  or  passive 
congestion  takes  place  in  the  tracheal  canal,  the  mucous  membrane  at 
the  level  of  the  tracheal  stricture  becomes  so  edematous  that  the  respi- 
ratory lumen  becomes  insufficient,  suffocation  follows,  and  death  may 
ensue. 

Relation  of  Goiter  to  the  Pharynx  and  Esophagus  (Plate  \  I  I. — In 
ordinal)'  goiters  the  pharynx  and  esophagus  are  seldom  involved.  Deglu- 
tition is  interfered  with  only  when  the  goiter  has  become  adherent  to 
the  walls  of  the  esophagus  either  because  of  a  strumitis  or  because  of  a 


124  ANATOMICO-PATHOLOGICAL  RELATIONS  OF  GOITER 

fibrous  or  malignant  goiter.  There,  too,  as  in  the  trachea  a  long,  con- 
tinuous pressure  on  the  esophageal  walls  may  cause  such  an  atrophy 
as  to  perforate  them,  and  yet  such  goiters  may  not  be  malignant  at  all; 
but,  of  course,  this  is  rare. 

Relation  of  Nodular  Goiter  to  Bloodvessels  (Plate  VI). — In  large 
goiters  the  common  carotid  is  displaced  posteriorly  and  laterally;  it  may 
even  be  found  in  the  posterior  triangle  of  the  neck.  I  have  seen  it 
more  than  once  not  far  from  the  anterior  border  of  the  trapezius.  The 
carotid  is  then  found  enlarged,  has  sometimes  a  tortuous  course,  is 
subcutaneous,  and  is  felt  as  a  tense,  expansive  cord. 

When  the  common  carotid  has  contracted,  intimate  relations  with 
the  capsule  of  the  gland,  on  account  of  strumitis  or  for  any  other  rea- 
son, this  posterolateral  displacement  of  the  vascular  trunk  is  easily 
understood;  yet  such  displacements  happen  in  goiters  in  which  no 
inflammation  whatever  is  found.  It  then  finds  its  explanation  in  the 
anatomical  relation  between  the  thyroid  gland,  the  common  carotid,  and 
the  superior  thyroid  artery-  In  undergoing  upward  enlargement  the 
goiter  seems  to  grow  in  the  angle  formed  by  the  carotid  and  the  superior 
thyroid  artery.  As  the  latter  is  firmly  fixed  by  its  two  terminal  branches 
to  the  thyroid  it  holds  tightly  the  common  carotid  to  the  posterolateral 
surface  of  the  goiter  in  the  same  manner  as  if  someone  should  carry 
somebody  on  the  back  or  over  the  shoulders  by  holding  him  tightly  by 
the  arm.  The  more  the  goiter  grows,  the  tighter  becomes  the  relations 
between  the  goiter  and  carotid,  consequently  the  more  the  carotid  will 
be  displaced  laterally  and  posteriorly.  At  the  same  time  it  becomes 
elongated;  in  voluminous  goiters  this  elongation  of  the  common  carotid 
may  be  sometimes  quite  marked.  Wolfler  saw  a  case  in  which  the 
carotid  formed  around  the  goiter  a  segment  of  a  circle  whose  radius 
was  6  cms. 

The  displacement  outward  of  a  carotid  has  a  very  important  diag- 
nostic value,  because  it  is  caused  by  goiter  and  by  nothing  else.  In 
tuberculosis  or  malignant  tumors  of  the  cervical  lymph  nodes  the  common 
carotid,  instead  of  being  displaced  outward,  lies  in  the  center  of  the 
tumor.  Again,  anatomy  will  give  us  the  reason  for  it:  normally,  the 
lymph  nodes  are  found  all  around  the  vascular  cord  of  the  neck,  conse- 
quently in  tumors  of  the  cervical  ganglions  the  common  carotid  must 
naturally  lie  in  the  middle  of  the  tumor. 

The  superior  thyroid  artery  loses  its  normal  anatomical  relations  only 
in  large-sized  goiters.  In  that  case,  very  much  increased  in  size,  this 
artery  follows  a  sinuous  course,  separated,  to  a  more  or  less  extent, 
from  its  normal  anatomical  neighbors,  namely,  the  inferior  constrictor  of 
the  pharynx  and  the  superior  laryngeal  nerve.  The  point  of  election 
for  its  ligation  is  the  superior  pole. 


RELATION  OF  GOITER   TO  NERVES  125 

Lving  directlv  on  the  prevertebral  fascia  the  inferior  thyroid  artery 
may  be  easily  compressed  and  displaced  by  a  growing  goiter.  In  partly 
intrathoracic  goiters  this  artery  is  covered  entirely  by  the  tumor  and  is 
consequently  of  difficult  access  for  ligation.  As  a  rule  the  safest  place 
to  ligate  the  inferior  thyroid  artery  is  inside  the  carotid  sheath,  between 
this  sheath  and  the  thyroid  gland.  The  ligation  of  the  artery  near  its 
point  of  entrance  into  the  thyroid  is  dangerous,  inasmuch  as  the  para- 
thyroids and  the  inferior  laryngeal  nerve  might  easily  be  injured. 

In  large  goiters  the  veins  of  the  neck  are  distended  because  the 
return  flow  of  blood  is  impaired  by  compression  on  the  large  venous 
trunks  or  because  of  some  pathological  disturbances  in  the  right  heart; 
as  a  result  of  it  an  intense  venous  congestion  is  seen  in  all  the  cervical 
region — the  anterior  jugular  vein,  the  superior  thyroid,  the  imce  veins, 
and  all  the  capsular  veins  may  be  so  distended  that  the  gland  seems 
to  be  the  site  of  an  angioma.  These  imae  veins  must  be  known  to  the 
surgeon,  as  they  are  the  ones  most  apt  to  allow  an  air  embolism.  In 
all  these  conditions  the  distended  veins  are  friable  and  thin.  They 
have  lost  their  elasticity:  hence,  the  frequent  venous  parenchymatous 
hemorrhages  which  may  sometimes  become  alarming. 

Relation  of  Goiter  to  Nerves  (Plate  VI). — The  nerves  which  are 
mostly  involved  in  voluminous  goiters  are  the  vagus  and  the  sympathetic. 
Compression  on  the  vagus  trunk  itself  does  not  give  rise  to  any  special 
symptoms.  Its  branch,  the  superior  laryngeal  nerve,  even  when  materi- 
ally compressed  and  displaced,  does  not  cause  appreciable  functional 
disturbances.  On  the  contrary  a  slight  injury  to  the  inferior  laryngeal 
nerve,  which  is  another  branch  of  the  vagus,  has  the  most  unpleasant 
consequence,  as  it  may  mean  for  the  patient  total  loss  of  voice.  After 
thyroidectomy  this  symptom  may  be  the  only  living  witness  of  the 
awkwardness  or  ignorance  of  the  surgeon.  As  a  rule  this  nerve  is  com- 
pressed in  the  inner  and  posterior  angle  of  the  tumor,  and  as  a  result 
of  this,  paralysis  of  the  corresponding  vocal  cord  may  follow.  I  he 
same  thing  may  happen  if  the  goiter  has  been  the  site  of  a  hemorrhage 
or  strumitis,  because  the  nerve  becomes  adherent  to  the  capsule:  hence 
again  causing  functional  disturbances. 

That  the  sympathetic  nerve  may  be  invoked  in  large  growing  goiters 
is  made  clear  by  its  anatomical  relations.  It  may  Income  compressed 
on  the  prevertebral  surface  or  it  may  be  constantly  traumatized  with 
each  pulsation  of  the  inferior  thyroid  which  comes  in  contact  with  it 
and  the  middle  cervical  ganglion.  Traumatism  of  the  cardiac  branches 
of  the  sympathetic  may  account,  too,  for  some  forms  of  tachycardia. 

The  hypoglossus,  spinal,  and  phrenic  nerves  and  the  cervical  and 
brachial  plexus  may  be  involved,  too,  by  the  large  growth  of  the  goiter. 


CHAPTER   VII. 

CLINICAL   SYMPTOMS   AND   DIAGNOSIS. 

CLINICAL    SYMPTOMS    OF    GOITER. 

A  great  many  goiters,  at  least  for  a  considerable  period  of  time, 
have  no  history.  They  do  not  betray  their  presence  by  any  mechanical 
or  functional  symptoms.  In  their  early  stage,  when  symmetrically 
placed,  they  give  to  the  neck  a  soft  roundness  called  "swan-neck,"  and 
considered  in  many  countries  as  one  of  the  attributes  of  feminine  beauty. 
Many  of  the  great  artists  of  the  past  centuries  shared  the  same  views, 
as  one  can  easily  convince  himself,  if  he  care  to,  by  visiting  certain 
museums.  Although  sometimes  a  slight  apathy,  thickening  of  the  tegu- 
ments, constipation,  chilliness,  etc.,  indicate  a  slight  degree  of  thyroid 
insufficiency,  while  in  other  cases  a  slight  tachycardia,  nervousness, 
impatience  in  disposition,  abruptness  of  movements  and  brilliancy  of 
the  eyes  betray  the  first  symptoms  of  hyperthyroidism,  these  patients 
are  absolutely  unaware  of  their  condition  and  would  sneer  at  one  who 
would  tell  them  that  they  are  sick. 

At  the  time  of  puberty  especially,  and  later  on  with  each  menstrual 
period,  young  girls  often  complain  of  constriction  of  the  neck,  of  chok- 
ing sensation,  of  coughing  spells;  during  sleep  they  are  frightened  with 
distracting  nightmares;  in  daytime  they  easily  get  tired,  complain  of 
palpitation,  nervousness,  tremor,  etc.  All  these  symptoms,  partly 
mechanical,  partly  thyrotoxic,  are  due  to  a  slight  parenchymatous 
goiter  which  so  often  accompanies  puberty.  In  the  great  majority  of 
cases  they  subside;  in  others,  however,  they  progress  and  evoluate  into 
a  permanent  parenchymatous  or  nodular  goiter,  be  it  toxic  or  not. 

A  goiter  may  cause  mechanical  and  functional  symptoms. 

Mechanical  Symptoms. — The  mechanical  disturbances  can  be  easily 
foretold  after  our  study  of  the  relations  of  a  goiter  with  the  neighboring 
tissues.  We  must  remember  that  the  symptoms  are  not  always  in  direct 
proportion  to  the  size  of  the  goiter;  a  small  median  or  retrosternal  goiter 
will  cause  far  more  serious  symptoms  than  a  voluminous  goiter  hanging 
in  front  of  the  thorax. 

Dyspnea. — One  of  the  main  symptoms  which  causes  the  patient  to 
seek  medical  attention  is  dyspnea.     It  may  be  produced: 

I.   By  direct  pressure  on  the  trachea. 


DYSPHAGIA  127 

2.  Bv  an  injury  of  the  inferior  laryngeal  nerve,  causing  paralytic 
conditions  of  the  vocal  cords. 

3.  Bv  venous  congestion  of  the  cervical  region  and  the  upper  part 
of  the  mediastinal  space  following  pressure  upon   the  nervous  trunks. 

Dvspnea  is  a  slow-developing  symptom.  For  a  long  time  the  patient 
is  not  aware  that  he  is  getting  out  of  breath  easily,  that  while  talking 
he  must  stop  frequently  to  draw  a  deep  breath  of  air.  In  time  he  becomes 
conscious  that  he  is  no  longer  able  to  climb  up  stairs  or  to  do  any  physi- 
cal exercise  without  losing  his  breath.  Gradually  respiration  becomes 
more  and  more  laborious,  and  when  finally,  on  account  of  pressure,  the 
lumen  of  the  trachea  has  become  greatly  narrowed  a  long,  loud,  whist- 
ling inspiration  is  heard:  that  is  the  tracheal  stridor.  Stridor  is  mostly 
inspiratory,  but  may  be  expiratory  also.  Dyspnea  may  be  constant  or 
paroxystic.  When  the  trachea  is  greatly  constricted,  a  slight  physical 
exertion,  a  simple  movement  of  the  head,  or  a  catarrhal  congestion  of 
the  laryngotracheal  tube,  or  any  sudden  pressure  from  without,  is  suffi- 
cient to  cause  attacks  of  asphyxia.  When  compression,  even  of  moderate 
degree,  is  of  years'  standing,  a  permanent  congestion  of  the  entire 
respiratorv  apparatus  takes  place,  and,  as  a  consequence  of  this  catarrhal 
condition  and  of  the  tracheal  stenosis,  emphysema  and  bronchiectasy 
develop.  Furthermore,  when  the  blood  circulation  in  the  lower  por- 
tion of  the  lungs  becomes  sluggish,  there  is  a  marked  tendency  to  bron- 
chitis, bronchopneumonia,  etc.  As  the  result  of  pressure  upon  the  large 
cervical  and  intrathoracic  venous  trunks,  stasis  takes  place  in  all  the 
upper  venous  system,  hence  vertigo,  headache,  congestion  of  the  face, 
nose-bleeding,  somnolence,  etc.  Like  stridor,  dyspnea  is  more  frequently 
inspiratory  than  expiratory. 

Dysphagia.  Difficulty  in  swallowing  is  especially  noticeable  in  the 
retrovisceral  and  intrathoracic  goiters.  The  patient  seldom  complains 
of  pain  in  swallowing;  he  may,  however,  have  some  difficulty  in  swal- 
lowing solid  food,  yet  in  uncomplicated  goiters  an  absolute  impossibility 
of  doing  so  is  not  known. 

The  voice  in  large  goiters  is  characteristic;  it  has  a  thick,  guttural, 
impure  tone,  as  if  the  vibrations  were  muffled.  1  his  is  due  to  the  con- 
gestion of  the  mucous  membrane  of  the  laryngotracheal  tube  and  ro 
the  slight  displacement  of  the  points  of  insertion  of  the  vocal  cords. 
and  on  that  account  they  cannot  ring  true.  If  to  that  we  add  a  muscular 
insufficiency,  we  will  understand  why  dining  the  speech  of  markedly 
goiterous  patients,  changes  in  the  voice  appear  so  brusquely,  why  cer- 
tain sounds  are  not  uttered,  win  "slips  of  the  voice"  occur,  the  whole 
thing  making,  as  Berard  says,  a  motley  mixture  of  couacs  and  silences 
which  are  very  peculiar  and  characteristic.  Berard  considers  tin  111  as 
vocal  awkwardness.  Only  in  the  later  stages  are  they  due  to  paretic  or 
paralytic  conditions  of  the  vocal  cords  and  constitute  then  the  bitonal  voice. 


128  CLINICAL  SYMPTOMS  AND  DIAGNOSIS 

Symptoms  Due  to  Injury  of  the  Inferior  Laryngeal  Nerve. — Bilateral 
paralysis  of  both  inferior  laryngeal  nerves  is  found  only  in  malignant 
goiters.  In  the  benign  form  of  goiters,  injury  of  the  inferior  laryngeal 
nerve  is  nearly  always  unilateral;  it  then  determines  tonic  contractions 
of  the  vocal  cords  of  the  same  side,  which  give  to  the  voice  a  bitonal 
character.  It  may  cause,  too,  coughing  spells  and  spasm  of  the  glottis, 
which  may  be  so  marked  as  to  cause  the  most  alarming  symptoms  of 
suffocation.  Cough  of  recurrent  nerve  origin  differs  clinically  from  the 
one  resulting  from  compression  on  the  bronchotracheal  tube.  We  can 
say  with  Varay  that  they  constitute  two  distinct  types: 

1.  The  cough  of  recurrent  type. 

2.  The  one  of  compression  type. 

The  "recurrent  cough"  is  dry,  loud,  and  not  accompanied  with 
expectoration.  It  comes  on  mostly  by  spells.  The  "compression  cough" 
is  sonorous,  deep,  cavernous,  with  a  grave,  metallic  sound,  resembling 
the  cough  of  a  dog  choking  with  a  bone  in  his  throat;  it  is  really  a  "bark- 
ing cough."  Brought  on  by  slight  physical  effort,  it  does  not  seem  to 
annoy  the  patient  as  much  as  the  noise  would  indicate. 

When  compression  on  the  inferior  laryngeal  nerve  is  only  slight,  it 
manifests  itself  by  a  metallic  sound  of  the  voice,  due  to  a  paretic  condi- 
tion of  the  vocal  cord  involved.  As  long  as  the  inferior  laryngeal  nerve 
has  not  been  destroyed  the  patient  remains  exposed  to  sudden  and 
unexpected  spasms  of  the  glottis  because  the  constrictor  muscles  of  the 
glottis  resist  longer  than  the  dilatators;  the  latter  are  put  out  of  func- 
tion a  long  time  before  the  former.  On  the  other  hand,  when  the  pro- 
cess of  irritation  or  paralysis  of  the  recurrent  nerve  retrocedes,  as  Rosen- 
bach  and  others  have  shown,  the  dilatator  muscles  are  the  last  to 
recuperate  their  function. 

Paralysis  of  the  recurrent  nerve,  as  a  rule,  takes  place  gradually;  it 
may,  however,  be  sudden,  as  in  cases  in  which  a  brusque  compression 
due  to  an  intracystic  hemorrhage  occurs.  When  paralysis  of  the  nerve 
is  complete,  then  there  is  a  paralysis  of  the  corresponding  side  of  the 
glottis;  the  vocal  cord  of  the  paralyzed  side  takes  an  "intermediary" 
position,  and  as  the  vocal  cord  of  the  sound  side  does  not  go  beyond 
the  middle  line,  phonation  is,  of  course,  impossible;  hence  complete 
aphonia.  Later,  however,  the  sound  vocal  cord  increases  its  radius  of 
excursion,  swings  over  the  middle  line  in  order  to  come  into  contact  with 
the  paralyzed  cord:  aphony  then  disappears,  the  patient  may  even 
seem  to  have  regained  his  normal  voice;  his  singing  voice,  however, 
never  returns. 

In  goiter,  injuries  of  the  inferior  laryngeal  nerve  are  relatively  fre- 
quent. They  are  mostly  characterized  by  symptoms  of  slight  impor- 
tance, and  according  to  statistics,  the  frequency  of  such  lesions  varies 


IX JURY  OF   THE  IXFERIOR  LARYXGEAL  XERYE  129 

from  7  to  35  per  cent,  of  the  cases.  Lesions  of  the  inferior  laryngeal 
nerve  predominate  on  the  left  side  as  a  rule.  Avellis  found  that  out  of 
150  recurrent  laryngeal  paralyses,  46  were  on  the  right  side,  92  on  the 
left,  and  12  were  bilateral.  B.  Mathews  out  of  289  partial  or  complete 
paralyses  found  93  on  the  right  side,  162  on  the  left,  and  17  bilateral. 
Predominance  of  paralysis  on  the  left  side  may  be  accounted  for  bv  the 
fact  that  the  left  inferior  laryngeal  has  a  longer  course,  and  is  more 
exposed  to  pressure  not  only  in  the  mediastinal  space  but  also  in  the 
cervical  region,  as  it  is  more  superficial  than  the  right.  Although  the 
frequency'  of  pressure  symptoms  on  the  recurrent  nerves  is  in  direct 
proportion  to  the  size  of  the  goiter,  Mathews  found  some  exceptions: 
small  goiters,  hardly  large  enough  to  be  recognized,  may  produce  symp- 
toms of  paralysis,  whereas  large  ones  may  not  cause  any.  Men  are 
about  three  times  as  liable  as  women  to  have  paralysis  of  the  inferior 
laryngeal  nerves. 

The  trunk  of  the  vagus  nerve  itself  is  seldom  involved  bv  goiters 
except  in  strumitis  and  cancers.  In  rare  instances  the  slowness  of  the 
pulse  and  respiration  have  been  interpreted  by  some  authors  as  due  to 
mechanical  traumatism  of  the  vagus  nerves. 

So  far  as  the  sympathetic  nerve  is  concerned  it  is  not  always  easv  to 
recognize  clinically  the  symptoms  which  belong  to  mechanical  com- 
pression of  the  sympathetic  nerve  itself;  if,  however,  the  sympathetic 
symptoms  are  localized  on  one  side  of  the  face  only  then  the  diagnosis 
of  compression  on  the  sympathetic  side  can  be  made  with  certainty. 
1  he  symptoms  of  excitation  of  the  sympathetic  are  a  unilateral  exoph- 
thalmos with  dilated  and  sluggish  pupil,  enlargement  of  the  palpebral 
fissure,  and  redness  of  one  cheek  more  marked  than  the  other.  The 
symptoms  of  paralysis  are  ptosis  of  the  eyelid,  thus  producing  a  smaller 
palpebral  fissure,  myosis,  on  account  of  the  dilatator  muscles  of  the 
pupils,  redness  of  the  ear,  and  abundant  perspiration  on  the  paralyzed 
side. 

In  extremely  rare  cases  the  spinal  nerve  is  involved;  a  torticollis,  or 
wry-neck,  due  to  spasmodic  contraction  of  the  trapezius  and  sterno- 
cleidomastoid muscles,  is  then  the  consequence  of  it.  The  lesions  of  the 
hypoglossus  nerve  occur  only  in  goiters  developed  from  the  thyroglossus 
duct.  In  such  conditions  a  paresis  and  an  atrophy  of  the  corresponding 
side  of  the  tongue  have  been  observed.  Symptoms  of  compression  of  the 
superficial  cervical  plexus  are  found  sometimes  in  voluminous  goiters 
and  are  characterized  by  irradiating  pains  toward  the  auriculotemporal 
and  occipital  regions.  When  pressure  takes  place  on  the  deep  cervical 
plexus,  pectoral  neuralgia  and  painful  formications  along  the  arm  and 
hand  have  been  reported.  The  phrenic  nerve,  especially  in  retrosternal 
goiters,  may  be  caught  and  compressed  in  front  of  the  scaleni  muscles; 
9 


130  CLINICAL  SYMPTOMS  AND  DIAGNOSIS 

this  is  rare,  however.  In  such  conditions  hemispasm  of  the  diaphragm 
will  be  present,  followed  later  by  paresis  or  paralysis  of  that  muscle. 

Functional  Symptoms. — Functional  symptoms  can  be  divided  into 
two  large  classes:  the  symptoms  of  hypothyroidism  and  those  of  hyper- 
thyroidism.    They  will  be  studied  in  separate  chapters. 

The  goiter-heart  will  be  studied  in  a  chapter  by  itself. 


DIAGNOSIS    OF    GOITER. 

In  the  great  majority  of  cases,  diagnosis  of  goiter  presents  no  diffi- 
culty. First  of  all  the  history  of  the  patient  puts  us  at  once  on  the 
right  scent  by  telling  us  if  the  patient  comes  from  a  country  where 
goiter  is  endemic  or  not,  if  other  members  of  his  family  are  affected  with 
it  or  not,  or  if  he  complains  of  mechanical  or  thyrotoxic  symptoms. 
When  dealing  with  a  tumor  of  the  neck,  the  two  important  things  which 
we  have  to  decide  are: 

i.   Is  the  tumor  in  the  thyroid? 
2.  What  is  its  nature? 

i.  Is  the  Tumor  Developed  in  the  Thyroid? — Inspection  shows  the 
form,  volume,  and  position  of  the  goiter.  It  shows  the  condition  of 
the  skin  of  the  neck,  whether  there  is  any  congestion  of  the  face,  any 
collateral  circulation  on  the  neck  or  thorax,  any  dyspnea,  any  symp- 
toms of  irritation  or  paralysis  of  the  sympathetic,  or  whether  any 
thyrotoxic  symptoms  as  tremor,  exophthalmos,  etc.,  are  present. 

There  is  one  symptom  which  is  pathognomonic  for  tumors  of  the 
thyroid:  that  is,  the  up-and-down  movements  which  the  tumor  follows 
during  deglutition.  As  the  thyroid  is  intimately  connected  with  the 
cricoid  cartilage  through  its  suspensory  ligament,  the  tumor  is  bound  to 
follow  the  larynx  in  its  up-and-down  movements.  This  symptom  sel- 
dom fails.  Only  when  the  goiter  is  extremely  large  or  when  it  has  a 
long,  loose  pedicle,  these  up-and-down  movements  may  be  doubtful. 
But  even  then  a  little  trick  may  solve  the  problem.  By  placing  the 
patient's  head  in  hyperextension  and  asking  him  to  swallow,  it  would  be 
very  surprising  if  these  up-and-down  movements  are  not  obtained; 
exceptionally,  however,  when  the  tumor  has  developed  at  the  cost  of  an 
accessory  thyroid  gland,  or  when  a  malignant  tumor  or  a  strumitis  has 
walled  in  all  the  organs  of  the  cervical  region,  then  these  up-and-down 
movements  will  not  be  detected. 

Palpation  must  be  done  methodically.  We  must  begin  by  ascer- 
taining if  possible  the  exact  position  of  the  thyroid  and  cricoid  carti- 
lages and  the  trachea  to  see  if  they  are  displaced  on  one  side  or 
the  other.     When  that  is  done  the  two  lobes,  isthmus  and  pyramidal 


DIAGNOSIS  OF  GOITER  131 

process  are  carefully  investigated  separately,  their  consistency,  their 
surface,  their  mobility,  and  their  relation  to  surrounding  structures  being 
carefully  noted. 

We  shall  find  that  in  the  greatest  number  of  cases  the  goiter  is  more 
mobile  transversely  than  vertically,  that  during  deglutition  the  tumor 
slips  out  of  the  palpating  hand  to  follow  the  up-and-down  movements 
of  the  larynx.  We  must  then  endeavor  to  outline  the  inferior  limits  of 
the  tumor.  The  best  way  to  do  so  is  to  palpate  with  the  thumbs,  the 
palms  of  the  hands  and  fingers  reposing  on  the  shoulders.  The  patient 
is  requested  to  flex  his  head  forward  and  laterallv  in  order  to  relax  the 
muscles  of  the  side  subjected  to  examination.  This  facilitates,  too,  the 
palpation  of  the  retrosternal  region.  With  some  care  and  skill  it  will 
then  be  possible  to  fish  out  of  the  thorax  quite  a  number  of  partially 
intrathoracic  goiters  which  were  never  suspected  before.  When  a  goiter 
is  a  multinodular  one,  pressure  on  each  nodule  separately  may  reveal 
the  one  which  is  causing  most  of  the  pressure  symptoms. 

Palpation  will,  furthermore,  show  that  the  common  carotid  is  pos- 
sibly displaced  laterally  and  posteriorly;  in  that  case  it  is  felt  pulsating 
subcutaneously.  The  condition  of  the  superior  thyroid  arteries  is  ascer- 
tained. If  a  goiter  shows  pulsation,  we  must  determine  if  this  pulsation 
is  only  transmitted  or  if  it  is  really  an  expansive  one. 

Percussion  over  the  thorax  is  intended  to  show  if  there  is  a  dulness 
caused  either  by  an  intrathoracic  goiter,  a  thymus  hyperplasia,  or  any 
other  mediastinal  tumor.  It  conveys,  too,  some  information  as  to  the 
condition  of  the  lungs  and  the  size  of  the  heart. 

Auscultation  will  tell  us  if  a  systolic  murmur  is  present  oyer  the  gland, 
especially  at  its  upper  poles.  It  will  tell  us,  too,  if  there  is  compression 
upon  the  trachea  by  the  tumor.  In  that  case  we  shall  hear,  especially 
over  the  manubrium  sterni,  a  rough  inspiration  followed  by  a  prolonged, 
loud  expiration,  unmistakably  accompanied  with  tubular  breathing.  I 
consider  this  finding  as  an  excellent  sign  of  compression.  Finally, 
auscultation  will  inform  us  as  to  the  true  condition  of  heart  and  lungs, 
the  knowledge  of  which  is  of  the  utmost  importance  when  it  comes  to 
prognosis  and  treatment. 

Laryngoscopic  Examination.  Laryngoscopy  examination  shows  the 
condition  of  the  vocal  cords.  This  examination  should  be  made  as 
a  routine  procedure  before  operation,  if  only  as  a  protection  to  the 
surgeon  in  order  to  avoid  being  held  responsible  for  an  injury  to  the 
inferior  laryngeal  nerves  which  existed  prior  to  the  operation.  I  rache- 
oscopy  is  seldom  indicated. 

An  x-ray,  if  deemed  necessary,  will  then  terminate  the  examination 
and  corroborate  or  disprove  many  of  the  clinical  findings.  It  will  add, 
furthermore,  precious  information  about   the  size  of   the  intrathoracic 


132  CLINICAL  SYMPTOMS  AND  DIAGNOSIS 

goiter,  if  there  is  any,  about  the  displacement  and  compression  of  the 
windpipe,  about  the  presence  of  thymus  hyperplasia,  etc. 

2.  What  is  its  Nature? — When  once  we  have  decided  that  the  tumor 
is  of  thyroid  origin  we  must  then  decide  what  its  nature  is.  In  diffuse 
parenchymatous  goiter  the  gland  in  toto  is  enlarged,  of  firm  consistency, 
and  finely  granular.  The  gland  has  more  or  less  kept  its  normal,  gen- 
eral outlines  unless  the  diffuse  enlargement  should  affect  one  lobe  more 
than  the  other.  By  closer  examination  it  is  not  uncommon  to  find 
small  nodules  of  harder  consistency  spread  throughout  the  gland.  In 
colloid  goiters  the  gland  has  lost  its  regular  form,  and  colloid  degenera- 
tion is  more  marked  in  one  lobe  than  in  the  other;  hence  the  irregularity 
in  the  form  of  the  thyroid.  The  surface  is  lobulated,  nodular  on  account 
of  the  presence  of  colloid  nodules  of  different  sizes;  consistency  may  be 
firm,  but  in  cases  in  which  the  colloid  nodules  are  large  and  of  different 
volumes  the  consistency  may  vary  considerably,  being  firm  in  places, 
hard  in  others,  and  soft  in  others.  Fibrous  goiter  is  characterized  by  its 
hard  consistency,  and  differs  from  the  calcareous  goiter  by  its  small 
size,  though  this  is  not  always  the  case.  Cystic  goiter  is  not  difficult 
to  diagnose,  especially  when  it  has  attained  a  certain  size;  its  surface  is 
smooth,  the  tumor  is  mobile,  elastic,  or  fluctuating.  When  fluctuation 
is  present  the  diagnosis  of  cyst  is  almost  certain.  I  say  almost  certain 
because  a  pseudofluctuation  sometimes  seen  in  some  colloid  nodules 
may  lead  one  to  believe  that  he  has  to  deal  with  a  cystic  tumor  when 
such  is  not  the  case. 

Vascular  goiter  is  of  rare  occurrence  except  in  exophthalmic  goiters. 
In  that  case  the  diagnosis  is  easily  made.  In  genuine  vascular  goiter 
the  tumor  is  soft  and  can  be  reduced  in  size  by  compression.  A  marked 
vascular  murmur  is  heard  over  the  gland  and  especially  at  its  poles. 
Thrill  and  expansive  pulsation  are  present. 

In  a  great  majority  of  cases  the  differential  diagnosis  between 
goiter  and  any  other  condition  is  hardly  necessary.  When  the  tumor  is 
median,  a  cyst  developed  from  the  thyroglossus  duct  might  be  confused 
with  a  median  goiter.  But,  as  a  rule,  this  cyst  of  thyroglossus  duct 
origin  lies  in  exactly  the  middle  line  and  is  found  mostly  between  the 
hyoid  bone  and  the  thyroid  cartilages,  whereas  a  median  goiter  is 
situated  below  the  cricoid. 

Congenital  cysts  of  the  neck  of  thymic  origin  are  located  along  the 
anterior  border  of  the  sternocleidomastoid;  they  are  independent  of  the 
trachea  and  larynx  and  do  not  follow  their  up-and-down  movements 
during  deglutition.  The  same  is  true  of  tuberculous  glands;  their 
anatomical  relations,  their  consistency,  their  pathological  characters, 
and  the  history  of  the  development  of  the  disease  differ  entirely  from 
those  of  goiter. 


GOITER-HEART  133 

GOITER-HEART. 

That  there  exists  a  relation  between  goiter  and  the  heart  was,  of 
course,  observed  long  ago.  Rose  first  thought  that  the  goiter-heart 
in  connection  with  stenosing  goiters  was  due  to  pressure  of  the  blood- 
vessels on  the  thorax.  Kocher  not  only  admitted  this  fact  as  an  etiolog- 
ical factor,  but  added  that  impairment  of  the  respiration  was  also  a 
cause  of  goiter-heart,  and  called  it  dyspneic  goiter-heart. 

Schrantz  believed  that  goiter-heart  was  caused  by  venous  stasis  in 
the  thorax,  causing  a  hyperemia  of  the  heart  muscle,  and  consequently 
an  excitation  of  the  cardiac  ganglions:  hence,  increased  cardiac  activity, 
then,  hypertrophy,  dilatation,  and  degeneration  of  the  muscle.  Wolfler 
took  a  similar  view. 

Kraus  designated  as  goiter-heart  the  cardiovascular  symptoms 
caused  not  by  the  mechanical  pressure  but  by  the  exaggerated  function 
of  the  thyroid  gland  and  its  action  on  the  regulating  cardiac  apparatus. 
Kocher  shared  this  same  view  and  differentiated  this  goiter  from  the 
mechanical  goiter-heart.  To  Minnich  we  owe  an  excellent  contribution 
on  the  question  of  goiter-heart  of  pneumonic  origin. 

There  are  two  separate  and  distinct  varieties  of  cardiac  disturbances 
that  may  occur  in  connection  with  goiter,  the  mechanical  goiter-heart 
and  the  thyrotoxic  goiter-heart.  Kocher  distinguishes  a  third  form  which 
is  rare:  this  condition  of  the  heart  is  caused  by  compression  of  the 
large  vessels  and  nerves  by  a  large  goiter.  This  goiter  is  then  called 
cardiopathic  goiter. 

The  Mechanical  Goiter-heart. — It  is  easy  to  understand  that  being 
given  their  anatomical  relations  with  the  thyroid  gland,  the  vagus  and 
sympathetic  nerves  may  be  mechanically  traumatized  by  a  large 
goiter.  These  lesions,  however,  are  rare;  when  present  they  are  mostly 
unilateral.  Bilateral  compression  on  the  vagus  and  sympathetic  by  a 
simple  goiter,  to  my  knowledge,  has  never  been  observed  except  in  malig- 
nant goiters.  Far  from  me,  however,  be  the  idea  that  is  not  possible. 
Furthermore,  there  are  a  great  many  goiter-hearts  in  which  traumatism 
of  the  vagosympathetic  system  cannot  be  rightfully  incriminated  on 
account  of  the  small  size,  location,  etc.,  of  the  goiters.  It  we  stop  to 
consider  the  close  anatomical  relations  of  the  vagus  and  sympathetic, 
it  is  hardly  admissible  that  traumatism  can  center  its  effects  on  one 
nerve  and  not  on  the  other.  It  seems  to  me  that  both  must  be  injured 
at  the  same  time.  If  that  is  the  case,  since  the  vagus  is  a  moderator 
and  the  sympathetic  an  accelerator  of  the  cardiac  action,  these  two 
nerves  should  counterbalance  their  action.  It  is  true  that  nutation  with 
the  faradic  current  of  the  sympathetic  produces  physiologically  a  slight 
acceleration   of  the   cardiac   action,   whereas    the   same   nutation   ol    the 


134  CLINICAL  SYMPTOMS  AND  DIAGNOSIS 

vagus  produces  a  moderation.  Surgical  experience  shows,  on  the  other 
hand,  that  division  of  both  vagi  or  both  sympathetics  has  no  effect, 
or  very  little,  on  the  frequency  of  cardiac  action.  Goiter-heart  is  really 
the  appanage  of  goiter.  It  is  not  found  in  the  malignant  degeneration 
of  cervical  ganglions,  in  Hodgkin's  disease,  etc.,  where  certainly  the 
chances  for  having  an  involvement  of  the  sympathetic  and  vagus  are 
great.     Why  is  it  ? 

So  the  theory  that  considers  pressure  on  the  vagus  and  sympathetic 
nerves  as  the  etiological  factor  of  goiter-heart  is,  in  my  judgment  at 
least,  not  tenable. 

The  pressure  on  the  bloodvessels  of  the  thorax  as  advanced  by  Rose 
is  a  very  important  etiological  factor  of  goiter-heart.  It  causes  a  stasis 
in  the  thorax  combined  oftentimes  with  respiratory  disturbances,  so 
that  a  stasis  in  the  right  auricle  and  ventricle  is  the  natural  conse- 
quence of  it:  then  follows  a  dilatation,  and  after  more  or  less  time 
a  degeneration  of  the  heart  muscle. 

The  impairment  of  respiration,  as  Kocher  and  Minnich  have  pointed 
out,  may  also  cause  goiter-heart. 

In  order  to  understand  the  development  of  such  pathological  condi- 
tions we  must  study  the  physiology  of  respiration  and  circulation. 

Normally  there  is  in  the  thorax  a  negative  pressure.  This  negative 
pressure  is  always  constant,  and  is  never  reduced  to  zero  even  in  forced 
expiration.  The  consequence  of  it  is  that  the  extrathoracic  pressure  is 
higher  than  the  intrathoracic  one.  For  this  reason  the  blood  is  aspirated 
toward  the  thorax;  this  fact  is  called  the  thoracic  suction. 

During  diastole  the  heart  increases  actively  the  size  of  its  chambers, 
and  by  so  doing  creates  a  vacuum  which  produces  a  sucking  effect  on 
the  blood  of  the  tributary  vessels.  With  Minnich  let  us  call  that 
ventricular  suction. 

Thoracic  and  ventricular  suctions  are  two  of  the  main  factors  in  the 
thorax  which  aspirate  the  blood  toward  the  heart.  Of  course  other 
important  factors  come  into  play,  but  they  are  without  importance  so 
far  as  the  explanation  of  goiter-heart  is  concerned. 

During  inspiration  the  thorax  increases  its  capacity,  hence  the  nega- 
tive pressure  increases  and  consequently  the  thoracic  suction  increases, 
too.  During  expiration  the  thorax  contracts,  the  lungs  expel  the  air 
contained  in  the  alveoli;  as  a  result  the  negative  pressure  is  diminished, 
and,  ipso  facto,  the  thoracic  suction.  As  a  consequence  of  this  fact  there 
is  normally  during  inspiration  an  increased  quantity  of  blood  aspirated 
toward  the  right  auricle  and  ventricle.  During  expiration  this  quantity 
is  diminished. 

During  these  physiological  phases  the  quantity  of  blood,  and  conse- 
quently the  pressure  in  these  chambers,  would  soon  run  above  normal 


GOITER-HEART  135 

if  there  was  not  a  compensatory  process  to  prevent  such  excess.  This 
compensation  is  furnished  by  the  capillaries  of  the  lungs.  During 
inspiration  they  follow  the  expansion  of  the  lungs,  increasing  their 
capacity,  so  that  the  blood  running  toward  the  heart  is  partly  side- 
tracked. Bv  this  process  the  pressure  in  the  right  heart  is  maintained 
normal.     Minnich  called  this  fact  the  pulmonary  compensation. 

The  effects  of  respiration  on  the  left  heart  are  quite  different  and 
very  much  less  marked,  because  of  the  size  and  of  the  thickness  of  its 
walls;  however,  during  inspiration  the  pressure  in  the  left  auricle  and 
ventricle  diminishes  in  a  moderate  degree,  and  during  expiration  increases 
in  the  same  proportion. 

These  few  physiological  explanations  will  enable  us  to  understand 
what  happens  in  cases  of  stenosis  due  to  goiter  or  any  other  obstacle  to 
respiration. 

In  inspiratory  dyspnea,  when  a  patient  takes  a  deep  breath  in  order 
to  get  enough  air,  the  thorax  expands  to  the  maximum,  so  that  the 
negative  pressure  in  the  thorax  is  greatly  increased.  In  such  conditions 
the  blood  is  aspirated  toward  the  right  heart  with  great  speed,  but 
unfortunately,  on  account  of  the  goiter-stenosis,  the  lungs  do  not  follow 
the  expansion  of  the  thorax.  Consequently  the  capillary  bloodvessels 
of  the  lungs  do  not  dilate;  in  other  words,  pulmonary  compensation 
does  not  take  place;  the  blood  is  not  side-tracked  in  proportion  to  the 
stream  running  to  the  right  heart,  hence  the  dilatation  of  the  right 
heart.  The  consequence  of  this  is  that  the  pressure  in  the  pulmonary 
artery  diminishes,  and  as  a  result  there  is,  too,  a  diminution  of  pressure 
in  the  pulmonary  vein,  in  the  left  auricle,  and  in  the  left  ventricle.  It 
the  musculature  of  the  right  heart  is  still  in  good  condition  it  will  com- 
pensate by  overwork  the  rupture  in  the  balance  of  pressure  between 
the  right  and  left  heart,  and  we  shall  then  have  an  hypertrophy  of  that 
section  of  the  heart.  If  the  musculature  is  degenerated  we  shall  have 
failure  of  compensation  and  its  results. 

In  expiratory  dyspnea  during  the  effort  of  expiration  the  negative 
pressure  is  considerably  diminished.  For  this  reason  the  blood  is  kept 
back  in  the  tributary  veins:  the  volume  of  blood  coming  to  the  right 
heart  is  considerably  diminished,  but  with  the  following  inspiration  all 
this  blood  which  has  been  kept  back  flows  toward  the  right  auricle  and 
ventricle  and  would  soon  overwhelm  this  segment  of  the  heart  if  this 
compensation  of  the  lungs  did  not  take  place  and  side-track  the  surplus 
of  blood.  But  suppose  the  expiratory  dyspnea  is  of  long  standing,  caus- 
ing emphysema,  bronchiectasy,  and  chrome  catarrh  of  the  respirator] 
apparatus,  then  in  that  case  the  capillaries  of  the  lungs  undergo  patho- 
logical changes,  and  the  compensation  cannot  take  place  normally;  the 
right  heart  is  soon  overwhelmed  by  the  quantity  of  blood  running  into 


136  CLINICAL  SYMPTOMS  AND  DIAGNOSIS 

it,  and   the  consequence  is  a  dilatation  of  the  right  auricle  and   right 
ventricle. 

So  the  final  results  of  an  inspiratory  and  expiratory  dyspnea  are  the 
same;  they  cause  a  dilatation  of  the  right  auricle  and  right  ventricle, 
and  finally  disturb  the  whole  cardiac  svstem. 

Goiter-heart  has  an  insidious  development.  The  goiter  may  be 
present  for  many  years  before  the  patient  is  aware  of  the  changes  which 
are  going  on.  For  a  long  time  the  patient  does  not  notice  that  the  tone 
of  the  voice  is  changing  and  that  he  easily  gets  out  of  breath.  He  attrib- 
utes the  cause  of  all  his  troubles  to  chronic  catarrh  of  the  trachea  and 
lungs.  Later  he  complains  of  vertigo,  headache,  congestion  of  the  face, 
epistaxis,  palpitations,  dyspnea,  at  the  slightest  physical  effort;  edema 
and  anasarca  are  the  terminal  stages.  At  that  time  the  volume  of  both 
cardiac  chambers  is  markedly  increased,  caused  by  hypertrophy  and 
dilatation. 

In  the  early  stages  there  is  generally  a  slight  systolic  murmur  to  be 
heard  at  the  apex,  betraying  a  mitral  insufficiency  caused  bv  the  stasis 
in  the  small  circulation.  Later  the  second  tone  of  the  pulmonary  valve 
becomes  weak.  In  late  stages  systolic  and  diastolic  murmurs  may  be 
heard  on  all  its  orifices.  Arrhythmia  is  present.  The  liver,  spleen,  and 
kidneys  become  congested;  anasarca  terminates  the  scene.  By  this 
time  the  pathological  changes  in  the  heart  are  so  extensive  and  so  irrep- 
arable that  the  entire  therapeutic  arsenal  has  become  powerless. 

Goiter-heart  is  not  always  present  in  all  cases  of  stenosing  goiter. 
The  reason  must  be  found  in  the  resistance  of  the  heart  itself.  It  is  a 
well-known  fact  in  medicine  that  one  heart  may  resist  certain  patholog- 
ical conditions  better  than  another;  this  is  due  to  individual  resistance 
and  to  the  existence  or  non-existence  of  previous  or  concomitant 
intoxications  or  infections. 

The  influence  of  age  certainly  should  not  be  neglected.  Other  things 
being  equal,  a  young  heart  will  offer  more  resistance  than  an  old  one. 
The  majority  of  well-developed  cases  of  stenosis  come  on  between  the 
ages  of  forty  and  sixty;  consequently  the  pathological  changes  in  the 
heart  will  be  more  common  at  that  period  of  life. 

The  purely  mechanical  goiter-heart  is  not  frequent.  It  is  usually 
combined  with  thyrotoxic  goiter-heart. 

The  Thyrotoxic  Goiter-heart. — To  this  class  we  do  not  ascribe  only 
the  goiter-heart  found  in  the  well-developed  exophthalmic  goiter  but 
also  all  the  intermediate  stages. 

As  Wolfler  says:  "It  is  easy  to  go  progressively  from  a  simple  goiter 
to  a  well-marked  Graves'  disease:  goiter  with  tachycardia;  goiter  with 
tachycardia  and  tremor;  goiter  with  tachycardia,  tremor,  and  psychic 
disturbances;    goiter   with    tachycardia,    tremor,    psychic    disturbances, 


GOITER-HEART  137 

exophthalmos,  etc.,  until  we  get  the  complete  clinical  picture  of  a  well- 
developed  Graves'  disease."  The)'  are  only  different  stages  of  the  same 
process. 

The  thyrotoxic  goiter-heart  may  be  caused  by  any  kind  of  goiter. 
The  parenchymatous  goiter  is  the  most  common  cause,  but  a  cystic  or 
colloid  goiter,  even  a  cancerous  or  sarcomatous  goiter  may  give  rise  to 
a  thyrotoxic  goiter-heart.  Cystic  and  colloid  goiters  do  not  cause  a 
thyrotoxic  goiter-heart  as  such,  but  their  presence  seems  to  incite  the 
remainder  of  the  gland  to  overfunction.  In  such  cases  the  goiter  becomes 
"  Basedowified."  The  same  explanation  accounts  for  the  rare  cases  in 
which  exophthalmic  symptoms  develop  in  cancer  or  sarcoma  of  the 
thyroid  gland. 

The  fundamental  symptom  of  the  thyrotoxic  goiter-heart  is  the 
increased  heart  action.  This  symptom  never  fails.  It  is  found  in  the 
fruste  forms,  and  may  remain  for  a  long  time  after  the  patient  is  practi- 
cally cured  of  the  other  symptoms  of  exophthalmic  goiter.  In  some  cases 
the  patient  is  not  aware  of  the  increased  heart  action,  but  in  the  great 
majority  of  cases  he  complains  of  palpitations.  These  may  come  on 
gradually  or  by  spells.  Oftentimes  the  slightest  muscular  exertion 
increases  the  action  of  the  heart  considerably.  The  pulse  rate  may 
reach  120,  150,  and  frequently  more. 

The  heart  action  is  not  only  increased  in  frequency  but  in  intensity 
as  well.  Often  the  whole  cardiac  region  shows  a  pulsation,  and  the 
beating  at  the  apex  is  strongly  marked. 

After  a  longer  or  shorter  period  of  duration  of  the  disease  the  heart 
area  is  increased.  This  increase,  it  is  found,  involves  mostly  the  left 
ventricle.  The  apex  beat  is  outside  the  mammillary  line;  the  transverse 
diameter  of  the  area  of  cardiac  dulness  is  increased;  fluoroscopic  exami- 
nation confirms  these  clinical  findings.  The  heart  lies  transversely  on 
the  diaphragm.  In  a  later  stage  when  the  thyrotoxic  intoxication  is  far 
advanced  the  right  ventricle  shows  a  marked  dilatation  and  the  area  of 
cardiac  dulness  is  found  extending  1,  2,  3  cms.,  and  sometimes  4  cms., 
outside  of  the  right  sternal  edge. 

In  many  casts  I  have  been  surprised  to  find  the  difference  in  the  ana 
of  cardiac  dulness  before  and  after  exercise.  Before  exercise-  the  heart 
limits  were  only  slightly  increased,  but  after  exercise  they  were  consid- 
erably enlarged.  I  consider  this  symptom  very  valuable  before  an 
operation  to  show  the  resistance  of  the  heart  to  the  surgical  attempt. 
If  after  exertion  dilatation  of  the  heart  is  present,  and  it  the  In  ait 
action  increases  considerably,  and  especially  it  myocarditis  is  present, 
one  should  "Pray  the  Lord  before  attempting  the  operation." 

In  thyrotoxic  goiter-heart  the  pulse  is  frequently  soft,  and  dicrotism 
is  often  observed.      In   advanced   cases  the  pulse  may   become   regular. 


138  CLINICAL  SYMPTOMS  AND  DIAGNOSIS 

blood-pressure  mav  be  increased,  but  it  is  generally  normal.  When 
thyrotoxicosis  is  well  developed  the  carotid  arteries  are  distended  and 
beat  violently.  The  veins  are  enlarged,  too,  and  show  a  venous  pulsa- 
tion. This  vascular  erethism  is  not  due  to  the  cardiac  impulse,  but 
seems  to  be  merely  localized  in  the  vessels  of  the  head  and  neck,  because 
it  does  not  extend  to  the  abdominal  aorta  nor  to  the  radial  or  other 
arteries.  Oftentimes  the  patient  feels  the  pulsation  all  over  the  head 
and  complains  of  roaring  in  the  ears.  The  cardiac  impulse  may  be  so 
intense  as  to  shake  the  whole  body  synchronously  with  the  heart  beat. 

Palpation  of  the  neck  gives  a  thrill,  especially  over  the  thyroid 
arteries.  Auscultation  frequently  gives  a  systolic  murmur  not  only  just 
over  the  arteries  but  also  all  over  the  thyroid  gland.  This  murmur,  espe- 
cially in  the  supraclavicular  spaces,  is  sometimes  continuous,  and  forms 
what  we  call  the  "bruit  de  none."  The  thyroid  gland  shows  not  only 
a  transmitted  but  also  an  expansive  pulsation. 

As  a  rule  the  mechanical  goiter-heart  and  thyrotoxic  goiter-heart 
are  seldom  separated  clinically.  Of  course  there  are  goiter-hearts  which 
are  purely  of  mechanical  origin,  but  even  then  there  exists  between  the 
mechanical  goiter-heart  and  the  Basedow-heart  a  series  of  intermediary 
symptoms  which  are  caused  by  the  thyroid  hyperfunction,  and  are  con- 
sequently of  thyrotoxic  origin.  Therefore  the  etiology  of  thyrotoxic 
goiter-heart  and  of  Graves'  disease  is  the  same.  There  is  no  difference 
between  the  thyrotoxic  goiter-heart  described  in  the  chapter  on  Graves' 
Disease  and  the  one  complicating  any  colloid,  cystic  or  malignant  goiter. 
The  thyrotoxic  symptoms  disappear  with  thyroidectomy,  or  at  least  are 
greatly  benefited,  providing  the  operation  takes  place  before  the  cardiac 
muscle  has  become  irremediably  altered. 

These  facts  are  of  great  importance.  From  them  derives  the  first 
very  clear  indication:  if  a  goiter  cannot  be  cured,  or  at  least  held  back 
in  a  harmless  state  by  ordinary  medical  means,  it  should  not  be  allowed 
to  wait  until  the  thyrotoxic  and  vascular  symptoms  of  goiter  have  gone 
too  far  before  performing  thyroidectomy.  Furthermore,  these  facts  are 
of  great  diagnostic  value  and  of  great  help  to  the  surgeon  in  deciding  if 
the  operation  can  be  done,  also  how  and  when. 

When  in  goiterous  tracheostenosis  the  pathological  disturbances  in 
the  heart  and  in  the  small  pulmonary  circulation  have  not  damaged 
these  organs  to  such  an  extent  as  to  become  permanent,  surgical  inter- 
ference gives  brilliant  results.  More  than  once  I  have  seen  cases  of 
intrathoracic  goiters  with  marked  dyspnea,  venous  congestion  of  the 
cervical  region,  irregular  pulse,  headache,  vertigo,  etc.,  entirely  relieved 
of  all  these  symptoms  after  operation.  The  most  remarkable  case  was 
that  of  a  woman  with  a  totally  intrathoracic  goiter  displacing  the  aorta 
and  compressing  the  basis  of  the  heart.    This  patient  had  what  I  thought 


GOITER-HEART  139 

was  a  marked  degree  of  myocarditis.  To  my  surprise  the  day  following 
the  operation  the  pulse  had  become  regular  and  has  remained  so  ever 
since. 

But  when  a  dilatation  of  the  right  heart  has  already  taken  place, 
when  tachycardia,  arrhythmia,  congestion  of  the  liver,  spleen,  and  gen- 
eralized edema  are  present,  an  operation  in  such  cases  can  only  termi- 
nate by  failure,  and,  what  is  worse,  in  death.  This  is  so  true  that  when 
Kocher  reported  the  results  of  3000  operations  for  goiter  he  said  that 
the  only  real  danger  which  he  still  feared  in  goiter  operations  was  cardiac 
collapse.  His  advice  was  then  to  operate  a  goiter  as  soon  as  possible 
and  to  discard  any  thyroid  or  iodin  treatment  when  a  goiter-heart  was 
present. 


CHAPTER    VIII. 
INTRATHORACIC  GOITER. 

We  call  intrathoracic  goiter  a  goiter  which  lies  in  the  thorax.  That 
variety  of  goiter  may  be  partly  intrathoracic  or  totally  so.  If  we  should 
call  intrathoracic  every  goiter  whose  inferior  poles  dip  more  or  less  into 
the  superior  opening  of  the  thorax,  we  should  regard  as  intrathoracic 
many  goiters  not  worthy  of  that  denomination.  Such  goiters  do  not 
extend  down  into  the  mediastinal  space;  their  inferior  limits  can  be 
outlined  more  or  less  easily  during  swallowing  or  coughing.  We  apply 
to  such  a  class  of  goiters  the  name  struma  profunda  or  deep  goiter  (Fig. 
35)  and  reserve  the  term  of  partly  intrathoracic  (Figs.  32  to  36)  to  goiters 
whose  greater  portion  lies  in  the  mediastinal  space  and  whose  remaining 
portion  lies  in  the  cervical  region.  As  the  name  indicates  the  totally 
intrathoracic  goiter  (Figs.  39  to  41)  lies  completely  in  the  thorax;  now  and 
then  there  is  not  even  external  evidence  of  thyroid  enlargement  in  the 
cervical  region. 

Intrathoracic  goiter  takes  its  origin  either  in  the  lower  poles  of 
the  thyroid  or  in  the  isthmus;  more  seldom  it  develops  in  accessory 
thyroid  glands.  When  originating  from  the  lobes  or  isthmus  the  intra- 
thoracic goiter  remains,  as  a  rule,  connected  with  the  body  of  the  thy- 
roid by  a  pedicle;  if  it  develops  from  an  accessor)'  thyroid  gland  it  has 
no  relation  whatsoever  with  the  thyroid.  These  latter  forms  of  goiter 
are  rare.  Intrathoracic  goiter  does  not  seem  to  develop  oftener  in  the 
lobes  than  in  the  isthmus. 

A  goiter  has  a  tendency  to  become  intrathoracic  for  three  chief 
reasons: 

1.  The  thyroid  gland  normally  goes  up  and  down  with  respiration, 
with  swallowing  and  coughing,  hence  the  tendency  to  drop. 

2.  The  goiter  is  more  or  less  forced  into  the  thorax  by  the  various 
movements  of  rotation  and  especially  by  flexion  of  the  head. 

3.  By  the  natural  action  of  gravity. 

In  short-necked  people  with  a  well-arched  thorax  the  thyroid  lies 
abnormally  low,  and  a  goiter  developed  in  that  gland  is  bound  to  become 
intrathoracic  very  soon.  This  abnormally  low  situation  of  the  thyroid 
has  been  called  by  Kocher  thyroptosis  (Fig.  43)  and  is  accompanied  at 
the  same  time  by  a  laryngoptosis.  According  to  von  Eiselsberg  this 
thyroptosis  is  frequently  found  in  patients  with  emphysema.      Kreuz- 


IXTRATHORACIC  GOITER  141 

fuchs  claims  that,  on  the  whole,  an  isthmoptosis  \s  more  frequently  found 
than  a  ptosis  of  the  entire  gland  itself.  In  rare  instances  the  isthmus 
seems  to  form  a  big  body  per  se,  being  connected  with  the  lobes  by  only 
a  thin  bridge  of  connective  tissue  containing  bloodvessels,  and  thus 
forming  what  Gruber  calls  glandule?  tripartita'.  In  such  glands  the 
isthmus  is  very  apt  to  sink  into  the  superior  opening  of  the  thorax  as 
soon  as  it  grows  in  volume. 

At  first  a  deep  goiter  extends  only  partly  behind  the  sternum  and 
underneath  the  first  rib.  It  moves  freely  up  and  down  with  the  larynx. 
Later,  when  the  goiter  has  descended  into  the  thorax  and  has  grown 
more  voluminous,  it  escapes  out  of  the  thorax  only  in  forced  respiration 
or  coughing.  But  as  the  goiter  continues  to  grow  there  finally  comes  a 
time  when  it  can  no  longer  escape  the  superior  opening  of  the  thorax; 
it  then  lies  in  the  superior  mediastinal  space  and  becomes  more  or  less 
completely  intrathoracic;  in  such  conditions  the  up-and-down  move- 
ments with  the  larynx  have  more  or  less  lost  their  entire  amplitude. 

We  can  consequently  conclude  that  the  great  majority  of  intra- 
thoracic goiters  have  been  at  one  time  cervical:  only  the  ones  which 
originate  from  an  intrathoracic  accessory  gland,  or  which  are  developed 
at  the  cost  of  an  extremely  ptosed  isthmus  or  lobe,  are  intrathoracic 
from  the  start.  If  two  separate  nodular  goiters  in  the  same  individual 
become  mediastinal  they  form  a  double  intrathoracic  goiter. 

Intrathoracic  goiters  vary  from  the  size  of  an  egg  to  that  of  a  large 
fist.  They  may  be  nodular  and  irregular  in  shape  when  they  are  formed 
by  an  aggregate  of  colloid  nodules,  but  they  may  also  have  a  smooth 
surface  with  a  round  or  oval  shape  when  formed  by  a  cyst  or  by  a 
unique  colloid  nodule.  Histologically  all  the  pathological  varieties  seen 
in  simple  goiter  are  found,  too,  in  intrathoracic  goiter. 

That  an  ordinary  goiter  dips  by  its  inferior  poles  more  or  less  low 
into  the  superior  opening  of  the  thorax  is  seen  quite  frequently,  and 
according  to  statistics  and  my  own  experience  it  occurs  in  about  25  to 
35  per  cent,  of  all  goiter  cases;  on  the  other  hand,  a  partly  intrathoracic 
goiter  occurs  in  about  15  to  18  per  cent,  of  the  cases.  In  this  class,  too, 
we  find  the  diving  or  plunging  goiter  which  has  been  so  well  described  by 
the  French  authors  and  called  goitre  plongeant.  This  plunging  goiter 
may  be  median  or  lateral;  it  owes  its  name  to  the  fact  that  at  times  it 
is  cervical  and  at  others  intrathoracic:  during  coughing  or  forced  expira- 
tion it  springs  up  suddenly  above  the  manubrium  sterni  and  then  disap- 
pears into  the  thorax  again.  Such  goiter  is  liable  to  become  incarcerated 
at  the  superior  opening  of  the  thorax  and  then  canst-  very  alarming 
suffocating  spells.  One  of  the  most  striking  specimens  of  plunging  goiter 
which  I  have  seen  was  while  1  was  the  assistant  to  my  master,  Kocher. 
It  was  developed    in   a  retroclavicular   accessory    thyroid    gland   on    the 


142  INTRATHORACIC  GOITER 

right  side,  had  no  connection  whatsoever  with  the  thyroid,  and  with 
each  coughing  used  to  play  in  the  most  exquisite  way  the  game  of  "Now 
you  see  me;  now  you  don't."  In  fact,  it  was  the  only  symptom  which 
had  brought  the  patient  to  seek  surgical  attention. 

Totally  intrathoracic  goiter  includes  all  cases  of  goiter  which  lie  in 
the  thoracic  cavity,  showing  no  signs,  more  or  less,  of  external  enlarge- 
ment of  the  gland.  This  is  the  true  intrathoracic  goiter.  It  occurs  in 
about  6  or  7  per  cent,  of  the  cases  of  goiter. 

Intrathoracic  goiter  may  in  rare  instances  be  congenital,  but  as  a 
rule  it  is  found  in  middle  age  about  the  fortieth  year  of  life.  My  young- 
est case  of  totally  intrathoracic  goiter  was  a  girl,  aged  about  thirteen 
years,  while  my  oldest  was  seventy-five  years.  It  is  more  frequently 
found  in  men;  it  is  of  benign  nature,  but,  of  course,  may  undergo  malig- 
nant degeneration.  As  ordinary  goiter  is  by  far  more  frequently  seen 
in  women  than  in  men,  it  may  seem  peculiar  to  find  intrathoracic  goiter 
more  frequent  in  men  than  in  women.  The  reason  is  that  men  begin 
hard  work  very  young  and  continue  it  all  their  life,  more  so  than  women. 
Hence  the  tendency  for  ordinary  goiter  to  become  intrathoracic. 

Intrathoracic  goiter  developed  in  the  isthmus  lies  in  the  middle 
line  and  is  called  the  median  intrathoracic  goiter  (Plate  VII,  Fig.  i).  A 
goiter  developed  in  one  of  the  lobes  lies  laterally  of  the  middle  line,  and 
for  that  reason  is  called  lateral  intrathoracic  goiter. 

Relation  of  Intrathoracic  Goiter  to  Neighboring  Tissues. — The  median 
intrathoracic  goiter  lies  in  front  of  the  large  vessels  and  is  bounded  by 
the  manubrium  sterni  in  front,  by  the  trachea  and  esophagus  behind, 
by  the  arch  of  the  aorta  or  innominate  artery  below,  and  laterally  by  the 
lungs.  The  lateral  intrathoracic  goiter  (Plate  VII,  Fig.  2)  is  bounded  in 
front  by  a  portion  of  the  sternum  and  costal  cartilages,  behind  by  the 
first  three  vertebrae  with  their  costal  insertions,  inwardly  by  the  trachea 
and  esophagus,  and  laterally  by  the  pleural  membrane.  A  very  impor- 
tant relation  of  intrathoracic  goiter  is  its  relation  to  the  large  intra- 
thoracic vessels;  it  may  he  in  front,  which  is  less  frequent,  or  behind 
them  or  laterally  too;  the  median  intrathoracic  goiter  nearly  always  lies 
in  front  of  these  vessels.  When  situated  behind  the  vessels  it  is  called 
retrovasal;  when  in  front  of  them  it  is  called  prevasal. 

In  conclusion  we  may  say  with  Wolfler  that  the  portion  of  the  thorax 
in  which  intrathoracic  goiters  can  be  found  is  limited  in  front  by  the 
manubrium  sterni  and  the  adjacent  portions  of  the  clavicles  and  of  the 
first  three  ribs;  behind,  by  the  first  three  thoracic  vertebrae  with  their 
costal  insertions;  laterally,  by  the  parietal  pleura;  below,  by  the  arch  of 
the  aorta,  the  innominate,  and  the  basis  of  the  heart;  above,  by  the 
superior  opening  of  the  thorax.  From  this  it  follows  that  an  intratho- 
racic goiter  may  come  in  contact  with  very  important  organs,  such  as 


PLATE    VII 


Relation  of  a  Median    Intrathoracic  Goiter  to    the    Surrounding 

Structures. 


Cross-section  of  the    Upper  Part  of  the  Thorax,  Showing   Relation  of" 
a  Lateral    Intrathoracic   Goiter  to  Surrounding  Structures. 


SYMPTOMS  143 

the  right  and  left  innominate  artery  and  veins,  the  common  carotids, 
the  arch  of  the  aorta,  the  basis  of  the  heart,  the  thoracic  duct,  both 
vagi,  the  inferior  laryngeal,  phrenic  and  sympathetic  nerves,  the  trachea 
and  the  esophagus.  On  account  of  such  dangerous  vicinity  it  will  be 
easilv  understood  that  intrathoracic  goiter  may  have  a  most  striking 
symptomatology. 

In  intrathoracic  goiter  as  well  as  in  cervical  goiter  the  trachea  may 
be  displaced  or  compressed,  or  both  together.  If  the  pressure  is  of  long 
standing  the  walls  of  the  trachea  may  become  atrophied.  In  median 
intrathoracic  goiter,  pressure  takes  place  anteroposteriorly.  In  lateral 
intrathoracic  goiter,  pressure  takes  place  laterally.  If  the  windpipe  is 
compressed  laterally  on  each  side  by  two  nodular  goiters,  compression 
may  be  so  marked  that  the  two  walls  of  the  trachea  may  come  in  con- 
tact with  each  other  and  form  what  we  call  the  sabre-sheathed  trachea 
(Fig.  27).  If  the  two  nodular  goiters  are  at  different  levels  then  the 
trachea  assumes  an  "S"  shape  (Fig.  28).  Beside  the  trachea  the  goiter 
mav  exert  pressure  on  one  of  the  main  bronchi.  More  seldom  com- 
pression of  the  upper  portion  of  the  lungs  may  be  found.  Kreuzfuchs 
more  than  once  had  opportunity  to  determine  such  compression  with 
the  jv-rays.  In  one  of  my  cases  compression  on  the  right  lung  was  so 
marked  and  had  been  of  such  long  standing  that  gangrene  of  the  apex 
followed  and  caused  an  empyema. 

All  the  large  vessels  of  the  thorax,  even  the  superior  vena  cava, 
aorta  and  basis  of  the  heart,  may  undergo  compression  and  displace- 
ment from  intrathoracic  goiter.  Thus  on  fluoroscopic  examination  the 
tumor  mav  appear  to  pulsate  and  may  then  be  taken  for  an  aneurysm. 
Yet,  closer  examination  will  show  that  this  pulsation  is  not  an  expan- 
sive one,  but  is  only  transmitted  by  the  aorta  or  the  other  large  vessels 
of  the  mediastinal  space. 

Injury  to  the  inferior  laryngeal  nerve  happens  more  frequently  on 
the  left  than  on  the  right  side.  Wolfler  thinks  this  is  due  to  the  fact 
that  the  left  inferior  laryngeal  nerve  is  more  superficial  than  the  right. 
That  may  be  true  in  some  cases;  in  others,  however,  Kienbock's  explan- 
ation is  more  satisfactory.  In  his  judgment,  as  the  intrathoracic  goiter 
presses  and  displaces  the  aorta  toward  the  left  side,  it  puts  the  inferior 
laryngeal  nerve  on  the  stretch,  hence  the  injury  to  the  recurrent  nerve. 
This  is  to  be  expected,  as  we  know  experimentally  that  traction  on  the 
nerve  is  the  equivalent  of  compression. 

Symptoms. — The  symptoms  produced  by  intrathoracic  goiter  do  not 
differ  in  any  way  from  those  described  in  conjunction  with  cervical 
goiter,  except  that  they  may  be  more  intense  and  that  suffocating  spells 
may  be  caused  by  the  slightest  physical  effort,  or  come  on  spontaneously, 
especially    dining   the   night.      While   in    bed    the   patient   cannot   find    a 


144  INTRATHORACIC  GOITER 

comfortable  position  for  sleep  as  the  recumbent  position  causes  a  con- 
gestion of  the  cervical  region,  soon  followed  by  suffocation;  on  the  other 
hand,  pillows  are  of  no  use  because  they  flex  the  head,  causing  the  chin 
to  press  upon  the  goiter  which,  in  turn,  compresses  the  trachea,  hence 
again  bringing  about  suffocation.  Such  patients  spend  their  nights  in 
an  arm-chair  like  asthmatic  or  cardiac  patients.  In  one  of  my  patients 
dyspnea  was  so  marked  that  I  had  to  operate  on  her  in  a  sitting  posi- 
tion, and  had  to  keep  her  in  that  position  until  the  goiter  was  fished 
out  of  the  thorax.  When  dyspnea  is  intense  there  is  during  inspira- 
tion a  sucking-m  of  the  suprasternal  and  the  epigastric  regions;  this 
phenomenon  is  called  by  the  French  authors  tirage. 

In  intrathoracic  goiter  the  auscultative  findings  differ  naturally  with 
the  situation — the  volume  and  the  relation  of  the  goiter  with  the  neigh- 
boring tissues.  If  a  bronchus  of  secondary  importance  only  is  com- 
pressed, respiration  in  the  corresponding  portion  of  the  lung  will  be 
diminished  in  proportion  to  the  compression.  If  one  of  the  main  bronchi 
is  totally  compressed,  a  complete  silence  will  be  found  in  all  the  cor- 
responding regions  of  the  lungs.  If  stenosis  of  the  tracheobronchial 
tube  is  incomplete  a  loud,  whistling  inspiration  and  a  prolonged  expira- 
tion with  tubular  character  will  be  found,  especially  over  the  sternum 
and  on  the  spine.  Emphysema  and  bronchial  catarrh  are  of  common 
occurrence.  If  the  lungs  themselves  are  compressed  there  is,  in  the 
area  of  pressure,  diminished  respiration  accompanied  with  rough  inspira- 
tion and  prolonged  expiration,  and  tubular  breathing.  More  than  once 
such  conditions  have  been  considered  as  incipient  tuberculosis. 

Certain  movements  of  the  head  increase  dyspnea,  whereas  certain 
others  afford  an  easier  respiration.  These  facts  soon  become  known  to 
the  patient  and  it  is  not  so  rare  to  find  a  patient  going  about  carrying 
his  head  always  in  the  same  posture,  as  if  he  were  suffering  from  a  boil 
on  the  neck.  When  of  long  standing  these  abnormal  positions  may 
even  produce  secondary  deformations  of  the  skeleton.  Kronlein,  for 
instance,  reported  a  case  in  which  intrathoracic  goiter  had  produced  a 
scoliosis  of  the  spine. 

A  symptom  which  is  considered  very  valuable  for  diagnosis  by 
Wolfler  and  Kocher  is  not  only  the  displacement  of  the  windpipe  later- 
ally, but  also  a  ptosis  of  the  larynx  in  toto  and  a  diminution  of  its 
up-and-down  movements:  the  radius  of  its  excursions  is  reduced  as  if 
something  were  trying  to  hold  it  immobile.  Laryngoptosis  may  some- 
times reach  such  a  degree  that  the  cricoid  cartilage  lies  at  the  level  of 
the  incisura  sterni  (Fig.  43).  Fixation  and  ptosis  of  the  larynx  are  of 
great  diagnostic  value  in  intrathoracic  goiter. 

Symptoms  of  compression  on  the  sympathetic  nerve  are  much  more 
frequent  in  intrathoracic  than  in  cervical  goiter. 


SYMPTOMS 


145 


Pressure  on  the  subclavian  and  innominate  veins,  and  on  the  superior 
vena  cava  produces  a  congestion  of  the  neck  and  head,  hence  roaring  in 
the  ears,  vertigo,  cyanosis,  etc.  In  some  cases  the  compression  of  the 
big  venous  trunks  is  so  marked  that  the  return  flow  to  the  heart  is 
greatly  impaired.  In  such  cases  a  collateral  circulation  is  established 
by  means  of  the  superficial  veins  of  the  thorax  and  inferior  portion  of 
the  neck;  the)-  become  distended  and  the  blood  reaches  the  heart  through 
the  superficial  anastomosis  which  joins  the  superior  and  inferior  caval 


Fig.   31.     Partially     intrathoracic    goiter 
wuli  a   marked  collateral  circulation. 


Fig.  32  I  Ik-  goiter  after  us  removal, 
I  Ik-  portion  below  the  clavicle  was 
intrathoracic. 


systems.  These  veins  mav  sometimes  attain  enormous  dimensions  and 
be  so  numerous  as  to  cover  the  entire  upper  portion  ot  the  thorax, 
forming  what  is  known  as  the  caput  medusa-  (Fig.  31).  The  arm  on 
the  corresponding  side  may  become  edematous.  In  some  rare  instances 
compression  on  the  large  arterial  trunks  may  diminish  or  suppress  the 
pulsations  of  the  carotid  and  radial  artery  on  the  side  involved,  lo  In- 
exact, I  must  say  that  these  symptoms  produced  by  the  interference 
of  the  arteriovenous  system  are  not  pathognomonic  of  intrathoracic 
goiter  only,  but  are  seen  in  any  sort  of  mediastinal  tumor. 
1(1 


146 


IN  TRA  THORA  CIC  GO  I TER 


The  intrathoracic  goiter  more  than  any  other  goiter  is  apt  to  cause 
cardiac  disturbances  and  give  rise  to  what  we  call  mechanical  goiter- 
heart,  wThich  is  often  combined  with  thyrotoxic  goiter-heart.  This  ques- 
tion has  been  thoroughly  discussed  in  the  chapter  on  Goiter-heart. 

Difficulty  in  swallowing  is  found  more  often  in  intrathoracic  goiter 
than  in  cervical  goiter.  These  disturbances  are  caused  not  only  because 
of  compression,  but  also  on  account  of  displacement  of  the  esophagus. 
Pressure  of  long  standing  on  the  esophagus  determines  chronic  inflam- 
matory conditions  in  the  musculature  and  in  the  esophageal  mucous 
membrane,  hence  the  difficulty  and  pain  which  the  patient  complains 
of  in  swallowing.     Interference  with  the  inferior  laryngeal  nerve,  whose 

branches  partly  supply  the  esopha- 
gus, may  sometimes  account,  too, 
for  much  difficulty  in  swallowing. 

Kreuzfuchs  and  other  authors 
have  described  a  symptom  which  is 
not  pathognomonic  for  intrathoracic 
goiter  alone,  but  is  very  often  found 
in  any  other  mediastinal  tumor;  it 
consists  in  the  forward  displacement 
of  the  manubrium  sterni.  Normally 
the  manubrium  and  corpus  sterni, 
although  sometimes  forming  a  slight 
angle,  are  on  the  same  level.  In 
intrathoracic  goiter  or  any  other 
mediastinal  tumor,  the  manubrium 
happens  not  infrequently  to  be  dis- 
placed forward  so  as  to  form  a  difference  in  the  level  between  the 
manubrium  and  the  gladiolus.  This  difference  may  vary  from  a  few 
millimeters  to  a  centimeter.  If  the  cartilages  of  the  first  and  second 
ribs  participate,  too,  in  this  forward  displacement,  the  whole  thing  forms 
a  characteristic  "moon-like"  picture  which,  according  to  Kreuzfuchs, 
is  more  often  seen  in  malignant  intrathoracic  goiter. 

Dulness  over  the  sternum  is  always  present,  except  in  a  few  cases 
in  which  the  intrathoracic  goiter  is  of  very  small  size  and  covered  by 
emphysematous  lungs.  Gentle  percussion  is  best  suited  to  bring  out 
the  outlines  of  intrathoracic  goiter.  As  a  rule  a  dulness  with  a  down- 
ward convexity  will  be  found,  a  point  of  good  differential  diagnostic 
value,  as  in  aneurysm  this  dulness  will  rather  show  an  upward  convex- 
ity. This  will,  of  course,  be  confirmed  by  the  x-rays.  Another  symptom 
of  great  diagnostic  value  is  the  displacement  of  such  dulness  by  forced 
respiration:  it  goes  downward  with  deep  inspiration  and  upward  with 
expiration.      As  a  rule  the  dulness  over  the  sternum  is  smaller  than  the 


Fig.  33. — Ten   days  after  the  operation. 


SYMPTOMS  147 

goiter  itself,  because  the  concomitant  emphysema  which  is  always 
present  in  tracheostenosis  prevents  the  outline  of  the  true  limits  of  the 
true  tumor.  In  lateral  intrathoracic  goiter  dulness  is  localized  over  the 
manubrium  sterni,  over  the  cartilages  of  the  second,  possibly  of  the  third 
rib,  and  over  the  sternoclavicular  articulation;  the  side  will  depend 
upon  which  side  the  goiter  has  originated.  If  the  intrathoracic  goiter 
is  median  the  dulness  will  be  found  mostly  over  the  manubrium  sterni. 

In  normal  individuals  auscultation  over  the  manubrium  sterni  will, 
as  a  rule,  show  a  faint  indication  of  respiration,  or  no  respiration  at  all. 
But  if  an  intrathoracic  goiter  is  interposed  between  the  sternum  and 
the  trachea,  and  with  still  greater  reason  if  the  trachea  is  compressed, 
auscultation  over  the  manubrium  sterni,  as  a  rule,  will  reveal  a  loud 
inspiration  and  a  prolonged  expiration  accompanied  with  marked  tubular 
breathing. 

X-ray  examination  should  really  become  a  part  of  the  routine  exam- 
ination in  anv  suspected  intrathoracic  goiter.  It  not  only  confirms  the 
clinical  findings,  but  completes  them.  Sometimes,  when  it  is  difficult 
to  decide  on  which  side  of  the  thorax  the  intrathoracic  goiter  is  located, 
A-rays  will  show  it.  The  fact  that  there  is  a  double  intrathoracic  goiter 
may  escape  clinical  detection;  the  v-ray,  however,  will  nearly  always 
give  you  this  information.  Furthermore,  it  gives  precise  indication  on 
the  situation,  form,  etc.,  of  the  trachea.  Finally,  it  may  prevent  the 
surgeon  from  overlooking  conditions  of  the  thoracic  organs,  which  may 
have  great  influence  on  the  success  of  the  operation,  such  as  tuberculosis, 
pleural  exudate,  etc. 

Normally,  in  the  dorsoventral  skiagram,  the  shadow  may  be  divided 
into  three  parts:   a  cervical,  a  mediastinal,  and  a  cardiac  shadow  (Figs. 

34  to  41)- 

In  intrathoracic  goiter  the  shadow  of  the  cervical  and  mediastinal 

portion  is  much  increased.  Laterally  the  shadow  may  reach  the  inner 
third  of  the  half  of  the  clavicle.  Downward  it  may  cover  the  base  of 
the  heart,  extending  to  the  middle  of  the  manubrium  sterni  and  to  the 
cartilage  of  the  third  rib.  Upward,  when  the  goiter  is  partially  intra- 
thoracic, it  extends  and  fuses  with  the  shadow  of  the  cervical  goiter. 
The  tone  of  the  shadow  of  the  intrathoracic  goiter,  as  a  rule,  is  regularly 
distributed,  dark  and  opaque;  its  contour  is  convexed  laterally  and 
sharply  marked,  as  a  rule,  because  of  the  contrast  with  the  shadow  ol 
the  lungs,  which  is  clear.  Instead  ol  being  regular  and  convexed,  how- 
ever, the  contour  may  be  undulated  and  irregular,  indicating  a  nodular 
goiter  or  a  malignant  tumor.  The  shadow  of  the  aorta  and  of  the  vena 
cava  may  be  absolutely  covered  by  the  goiter,  and  not  uncommonly 
the  arch  of  the  aorta  is  found  displaced  toward  the  left  side  and 
downward. 


148 


INTRATHORACIC  GOITER 


According  to  its  variety  the  shadow  of  the  intrathoracic  goiter  may 
be  median  or  lateral.      In  the  median  the  trachea  is  absolutely  covered 


Fig.  34. — Normal  skiagram  of  the  mediastinal  space. 


Fig.  35. — Skiagram  of  a  struma  profunda  or  deep  goiter. 


SYMPTOMS 


149 


Fig.  36. — Skiagram  of  a  partly  intrathoracic  goiter.     J,  intrathoracic  goiter;  B,  aorta. 


Fig.  37. — Skiagram  of  a  partly  intrathoracic  goiter.    Mote  compression  and  displacement 

of  the  windpipe. 


150 


TN  TRA  THORA  CIC  GO  I TER 


Fig.  38. — Skiagram  of  a  partially  intrathoracic  goiter. 


Fig.  39. — Skiagram  of  an  almost  totally  intrathoracic  goiter  from  patient  Fig.  40. 


SYMPTOMS 


151 


by  the  goiter  and  no  shadow  of  the  windpipe  is  seen  in  the  skiagram. 
In  the  lateral   intrathoracic   goiter  the  shadow  mav  be  mostly  devel- 


Fig.  40. — Almost  totally  intrathoracic  goiter.     Note  youth  of  patient  ( fourteen  years). 


Fig.  41.—  Skiagram  <>t  a  totally  intrathoracic  goiter:  ./,  intrathoracic  goiter;  B,  aorta. 

1  he  goiter  alter  removal  is  shown  in  lig.  42. 


oped  on  the  right  side  or  on  the  left  side  of  the  mediastinal  space,  accord- 
ing to  the  position  of  the  goiter.  In  that  case  the  aorta  may  be  seen 
displaced  toward  the  left  side,  tin-  windpipe  may  be  followed  more  or 


152  INTRATHORACIC  GOITER 

less  in  its  entire  course  and  may  be  displaced  or  compressed  or  may  be 
both  together.  In  a  few  instances  the  trachea  may  be  followed  to  its 
bifurcation. 

In  intrathoracic  goiter  not  only  skiagraphy  but  fluoroscopy  is  of  the 
utmost  importance.  A  fluoroscopic  examination  will  reveal  the  pulsa- 
tions, the  up-and-down  movements  of  the  goiter  during  inspiration  and 
deglutition.  The  shadow  of  the  goiter  is  not  infrequently  seen  pulsat- 
ing; these  pulsations,  however,  are  not  expansive,  but  are  transmitted 
from  the  neighboring  large  vessels,  especially  from  the  aorta. 

Up-and-down  movements  synchronous  with  the  act  of  swallowing  are 
pathognomonic  of  a  tumor  developed  in  the  thyroid  gland;  this  symp- 
tom never  fails,  except  in  an  abnormally  large  incarcerated  intratho- 
racic goiter  or  in  malignant  degeneration.  On  the  fluoroscopic  screen 
the  goiter  is  clearly  seen  rising  with  the  trachea  and  larynx,  but  the 
aorta  remains  immobile.  In  a  few  instances  the  aorta  is  seen  rising 
with  the  goiter;  this  does  not  mean,  however,  that  the  aorta  is  adherent 
to  the  goiter,  but  only  that  the  pressure  from  the  goiter  on  the  aorta 
being  released  the  normal  elasticity  of  the  aorta  brings  this  large  vessel 
into  its  normal  position  again.  The  best  way  to  observe  these  up-and- 
down  movements  is  to  have  the  patient  swallow  water,  or,  better,  to 
have  him  take  a  very  deep  inspiration,  hold  it  for  a  few  seconds,  and 
then  perform  a  quick  expiration.  In  so  doing  the  intrathoracic  goiter 
goes  downward  during  deep  inspiration  and  comes  upward  with  expira- 
tion. Sometimes,  according  to  Kreuzfuchs,  a  small  intrathoracic  goiter 
located  behind  the  manubrium  sterni  or  behind  the  sternoclavicular 
articulation  may  escape  notice  on  the  skiagram,  but  becomes  fluoro- 
scopically  detectable  while  the  patient  is  taking  a  deep  inspiration, 
because  the  nodule  emerges  laterally  from  the  shadow  of  the  sternum. 

Diagnosis. — The  diagnosis  of  a  partially  intrathoracic  goiter  is,  as  a 
rule,  not  difficult.  In  that  case  we  have  to  deal  with  a  patient  who  has 
had  for  a  longer  or  shorter  period  of  time  a  goiter.  He  complains  of 
dyspnea  and  palpitations,  and  more  recently  may  have  had  spells  of 
suffocation.  We  find  a  cervical  goiter.  Our  first  duty  is  to  outline  its 
inferior  limits.  If  we  do  not  succeed  we  ask  the  patient  to  cough  or 
to  swallow.  In  that  way  if  the  goiter  lies  only  behind  the  episternal 
notch  the  palpating  finger  will  be  able  to  outline  its  inferior  limits;  but 
if  the  goiter  extends  farther  down  we  shall  not  know  how  far  down  the 
goiter  reaches.  We  shall  have  to  rely  upon  percussion  and  ausculta- 
tion. We  must  see  if  there  is  any  congestion  or  puffiness  of  the  face; 
if  there  is  any  collateral  circulation  in  the  neck,  thorax,  and  arms;  if 
there  is  any  difference  between  the  radial  and  carotid  pulse  on  each 
side;  if  there  is  any  irritation  or  paralysis  of  the  sympathetic  nerve; 
any  fixation  or  ptosis  of  the  larynx;  any  displacement  of  the  windpipe, 


DIAGXOSIS  153 

or  any  difficulty  in  swallowing,  etc.  These  symptoms  and  the  x-ray 
picture  will  terminate  the  examination,  and  as  a  result  diagnosis  of 
partially  intrathoracic  goiter  will  always  be  made.  But  with  a  goiter 
which  is  totally  intrathoracic,  diagnosis  is  very  much  more  difficult. 
Here  we  shall  have  to  rely  mostly  upon  the   mediastinal  symptoms. 

The  first  thing  to  do  is  to  ascertain  that  the  thyroid  gland  is  in  its 
normal  position,  and  that  the  two  lobes  and  isthmus  are  normally  situ- 
ated, since  a  missing  lobe  is  a  feature  of  enormous  diagnostic  value. 
In  the  latter  condition,  Wiihrmann  claims  that  there  is  a  depression  of 
the  skin  between  the  sternocleidomastoid  muscle  and  the  larvnx. 

Another  symptom  of  great  importance  is  the  feeling  with  the  finger 
of  an  impact  above  the  episternal  notch  during  expiration,  swallowing, 
or  coughing.  This  impact  is  caused  by  the  intrathoracic  goiter  rising 
with  the  larvnx. 

The  presence  of  a  pedicle  extending  from  one  lobe  or  isthmus  down- 
ward behind  the  sternum  is  a  clue  of  great  diagnostic  value.  If,  further- 
more, the  palpating  finger  is  not  able  to  feel,  as  is  normally  the  case, 
the  tracheal  rings  of  the  windpipe  behind  the  episternal  notch,  but  finds, 
on  the  contrary,  a  mass  interposed  between  the  sternum  and  the  trachea, 
and  if  this  mass  moves  up  and  down  during  swallowing,  the  diagnosis 
of  an  intrathoracic  goiter  is  certain.  But  such  symptoms  as  those  above 
mentioned  may  not  be  present,  or  may  be  doubtful,  and  then  the  diag- 
nosis becomes  greatly  difficult.     In  such  cases  we  must  decide: 

i.  \\  hether  we  have  to  deal  with  a  mediastinal  tumor,  and  if  so, 
2.   \\  hat  is  its  nature  ; 

That  we  have  to  deal  with  a  mediastinal  tumor  will  be  shown  by 
the  subjective  symptoms  described  by  the  patient,  as  well  as  the  objec- 
tive ones  found  in  the  course  of  our  examination,  such  as  congestion; 
puffiness  of  the  face  and  neck;  collateral  circulation  of  the  thorax;  dimin- 
ution or  disparation  of  the  radial  pulse  on  one  side;  possibly  edema  of 
one  arm;  well-defined  dulness  over  the  upper  portion  of  the  thorax; 
forward  displacement  of  the  manubrium  sterni;  paresis  or  paralysis  of 
one  or  both  inferior  laryngeal  nerves,  and,  an  unmistakable  shadow 
on  the  skiagram.  These  mediastinal  symptoms  will  not  always  be  all 
pit-sent,  but  in  the  great  majority  of  cases  there  will  be  enough  of 
them   to  warrant  a  sure  diagnosis. 

When  once  the  diagnosis  of  mediastinal  tumor  is  made  with  cer- 
tainty, we  must  decide  if  we  have  to  deal  with  an  intrathoracic  goiter 
or  nor.  In  that  direction  the  history  of  the  patient  may  furnish  pre- 
cious indications.  lie  may  have  previously  had  a  goiter  which  has 
"disappeared."  Indeed,  it  is  not  infrequent  to  see  patients  who  believe 
that  they  have  been  cured  of  a  goiter  because  their  neck  seems  to  be 
free  from  it;  nevertheless  tin-  goiter  is  still  present  but  has  become 
intrathoracic. 


154 


INTRATHORACIC  GOITER 


The  symptoms  which  will  be  of  great  value  in  deciding  if  a  mediastinal 
tumor  is  a  goiter  or  not  are: 

i.  Dyspnea,  which  is  entirely  out  of  proportion  to  the  cervical  goi- 
ter, if  there  is  any,  or  with  the  size  of  the  mediastinal  tumor,  as  shown 


Fig.  42. — Totally  intrathoracic  goiter. 

by  the  skiagram  and  percussion.  The  suffocating  spells,  especially  at 
night,  speak  for  goiter,  as  also  does  the  fact  that  flexion,  or  extension, 
or  lateral  movements  of  the  head  increase  dyspnea  or  cause  suffocation. 


Fig.  43. — Intrathoracic  goiter  accompanied  with  thyro-  and  isthmoptosis. 

These  suffocating  spells  may  be  stopped  or  greatly  benefited  by  pulling 
the  larynx  upward  or  by  displacing  it  laterally;  on  the  contrary,  in  other 
conditions  these  procedures  may  accentuate  the  suffocating  spell. 


DIFFERENTIAL  DIAGNOSIS  155 

2.  A  ptosis  of  the  larynx,  and  diminution  of  the  radius  of  its  excur- 
sions, or  its  entire  fixation.  In  mediastinal  tumors  other  than  intra- 
thoracic goiter,  ptosis  and  fixation  of  the  larynx  are  less  frequently  seen. 

3.  The  absence  in  the  cervical  region  of  one  lobe  or  the  isthmus 
(Figs.  42  and  43).    This  symptom  is  of  great  diagnostic  value. 

4.  The  feeling  of  an  impact  behind  the  episternal  notch  when  the 
patient  swallows. 

5.  Stenosis  of  the  trachea  in  the  region  of  the  fifth,  sixth  or  seventh 
cartilaginous  rings  of  the  trachea,  detected  either  by  laryngoscopy  or 
tracheoscopy. 

6.  If  symptoms  of  hyperthyroidism  are  found  in  connection  with  this 
mediastinal  tumor,  as  tachycardia,  tremor,  exophthalmos,  nervousness, 
etc.,  the  chances  are  great  that  we  have  to  deal  with  an  intrathoracic 
goiter. 

7.  The  fluoroscopic  examination  will  be  of  enormous  value,  espe- 
cially if  it  is  able  to  show  the  up-and-down  movements  of  the  shadow 
synchronous  with  the  act  of  swallowing.  In  that  case  the  diagnosis 
becomes  certain. 

Differential  Diagnosis. — Sometimes  the  difficult)'  is  to  decide  whether 
we  have  to  deal  with  an  aneurysm  or  an  intrathoracic  goiter,  since  even 
fluoroscopic  examination  will  not  always  solve  the  problem.  Symptoms 
may  be  much  the  same  in  both  cases,  pulsations  being  transmitted  to  the 
intrathoracic  goiter  by  the  innominate  or  the  arch  of  the  aorta.  These 
two  conditions  have  been  mistaken  one  for  the  other  more  than  once. 
It  would  seem  that  in  doubtful  cases  auscultation  of  the  heart  and  aorta 
would  throw  the  necessary  light  upon  the  diagnosis,  yet  it  is  not  always 
so,  as  auscultation  of  an  aneurysm  may  be  entirely  negative. 

Here  the  physical  and  skiagraphic  examination  will  be  of  great  help. 
If  the  shadow  is  located  more  or  less  to  the  left  of  the  mediastinal  space 
the  diagnosis  between  aneurysm  and  intrathoracic  goiter  is  most  diffi- 
cult; but  if  it  is  located  to  the  right,  and  if  sympathetic  and  laryngeal 
nerve  symptoms  are  present  on  the  right  side,  too,  the  chances  are  great 
that  we  have  not  to  deal  with  an  aneurysm,  but  with  a  goiter,  unless 
we  should  be  unlucky  enough  to  meet  with  an  aneurysm  of  the  innomi- 
nate. Each  of  the  symptoms  above  mentioned  should  be  given  careful 
attention  and  its  relative  value  duly  considered  in  order  to  arrive  at  a 
safe  diagnosis. 

Kreuzfuchs  says  that  a  shadow  of  an  intrathoracic  goiter  differs 
from  the  shadow  of  an  aneurysm  by  the  fact  that  there  is  an  angle 
between  the  shadow  of  the  vessels  and  the  tumor,  and  that  at  the  fluoro- 
scopic examination  during  the  act  of  swallowing  these  two  shadows 
separate  from  each  other  in  the  case  of  goiter.  If  it  were  always  possible 
to  determine  on  the  fluoroscopic  screen,  if  pulsation  seen  in  the  tumor 


156 


IX  TRA  THORA  CIC  GOT  TER 


is  an  expansive  instead  of  a  transmitted  one,  diagnosis  would  then  be 
made  easier,  because  we  know  that  an  aneurysm  expands  in  every  direc- 
tion; whereas  in  transmitted  pulsations  such  a  movement  takes  place 
always  in  the  same  direction.  Unfortunately  this  is  not  always  possible; 
more  than  that,  one  may  come  against  cases  of  true  aortic  aneurysm 
where  no  pulsations  whatsoever  can  be  detected,  because  the  aneurysm 
is  accompanied  by  diffuse  inflammatory  or  syphilitic  mediastinitis. 
Lateral  fluoroscopic  examination  is  of  great  help  in  deciding  if  we  have 
to  deal  with  an  aneurysm  or  a  mediastinal  tumor,  because  in  the  latter 
condition  there  is  no  clear  space  between  the  spine  and  the  tumor, 
whereas  this  "clear  space"  exists  in  aneurysm  unless  the  aneurysmal 
sac  has  acquired  large  dimensions  and  a  pen-aortitis  due  to  frequent 
hemorrhages  has  taken  place. 

A  large  and  flat  aorta  might  be  mistaken  for  a  mediastinal  tumor, 
but  in  that  case  a  lateral  view  of  the  patient  will  clear  up  the  diagnosis. 


Fig.  44. — Lateral  radiogram  of  a  normal  heart: 
A,  spica;  B,  aorta;  C,  heart;  D,  diaphragm. 


Fig.  45. — Lateral  radiogram  of  an 
aneurysm. 


Syphilitic  or  tuberculous  mediastinitis  must  be  differentiated  from  the 
intrathoracic  goiter.  Both  varieties  of  mediastinitis  are  located  mostly 
in  the  posterior  superior  mediastinum,  whereas  intrathoracic  goiters  are 
seen  in  the  superior  anterior  mediastinum.  Skiagraphic  examination 
shows  that  in  mediastinitis  the  shadow  is  more  diffuse  and  somewhat 
linear,  whereas  the  shadow  of  a  goiter  is  more  round  and  convex  down- 
ward. In  tuberculosis  of  the  mediastinal  space  the  skiagram  will  show 
enlarged  tracheobronchial  glands  at  the  hilum  of  both  lungs.  In 
syphilitic  mediastinitis  (Fig.  46)  Wassermann  and  specific  treatment 
may  clear  up  the  diagnosis. 

Hypertrophy  of  the  thymus  may  have  to  be  differentiated  from  an 
intrathoracic  goiter.  This  thymic  hyperplasia  occurs  mostly  during  the 
early  years  of  life.     However,  in  adults  it  may  persist  and  is  especially 


DIFFERENTIAL  DIAGNOSIS 


157 


found  in  combination  with  goiter.  The  x-ray  picture  of  thymus  hyper- 
plasia is  absolutely  different  from  the  picture  of  intrathoracic  goiter. 
The  diagnosis  of  thymus  hyperplasia,  contrary  to  all  that  has  been 
written,  is  possible  in  a  great  majority  of  cases.  Clinical  examination 
must  be  always  accompanied  by  this  skiagraphic  examination. 

Normally  a  skiagraphic  mediastinal  shadow  (Fig.  34)  measures  from 
2.5  to  3.5  cms.  under  the  arch  of  the  aorta,  from  3  to  3.5  cms.  at  the  arch 
of  the  aorta,  and  from  5  to  6  cms.  at  the  conus  arteriosus.  The  shadow 
of  this  region  is  dark,  opaque,  and  regularly  distributed,  and  has  definite 
limits. 


FlG.   46. — Syphilitic  mediastinitis.     Note  the  location  of  the  shadow. 

In  thymus  hyperplasia  there  is  a  shadow  which  overlaps  laterally  the 
normal  mediastinal  shadow  (Figs.  47  and  48).  It  may  affect  one  lobe 
more  than  the  other,  or  may  affect  both  lobes  in  the  same-  proportion. 
The  thymic  shadow  is  more  or  less  triangular;  from  the  basis  ot  tin-  heart 
it  extends  upward  on  each  side  in  a  Straight  line,  or  follows  to  some 
extent  the  contour  of  the  mediastinal  shadow;  it  covers  the  auricles, 
which  seem  to  be  overdistended,  and  forms  an  angle  between  them  and 
the  ventricles;  hence,  too,  an  enlargement  of  the  auricles  which  is  not 
in  proportion  to  the  rest  of  the  heart.  The  character  of  this  thymic 
shadow  differs   from   the  cardiac   and   mediastinal   shadows.      It   is   thin. 


158 


INTRATHORACIC  GOITER 


transparent,   soft,   and   regularly   distributed;  its  edges,   as   a   rule,   are 
sharply  limited  and  linear. 


Fig.  47. — A,  intrathoracic  goiter;   B,   thymus   hyperplasia.      Findings  corroborated   by 

postmortem. 


Fig.  48. — A,  thymic  shadow. 


PROGXOSIS  159 

Prognosis. — The  prognosis  of  an  intrathoracic  goiter  depends  upon 
many  factors.  A  lateral  intrathoracic  goiter  may  sometimes  cause 
pulmonary  symptoms;  a  median  intrathoracic  goiter  will  compress  the 
trachea  anteroposteriorly,  and  consequently  give  dyspneic  symptoms 
much  earlier  than  the  former  one.  Compression  of  the  windpipe  and  of 
the  bronchial  tubes  cause  a  stubborn  catarrh  which  resists  every  medical 
treatment.  Intrathoracic  goiter  more  than  any  other  is  apt  to  cause 
choking  spells,  but  one  of  the  most  tragic  terminations  of  an  intrathoracic 
goiter  is  "sudden  death,"  which  will  be  discussed  in  the  chapter  on 
Goiter  Death. 

Even  free  of  symptoms,  an  intrathoracic  goiter  is  still  dangerous  to 
the  patient  because  a  hemorrhage  may  take  place,  an  acute  infection 
or  a  malignant  degeneration  may  develop  in  it,  and  so  endanger  the  life 
of  the  patient. 

In  skilful  hands  the  prognosis  of  the  cases  treated  surgically  is  excel- 
lent. Out  of  his  last  77  cases  of  intrathoracic  goiters,  Kocher  lost  but 
1  case.  Autopsy  showed  advanced  sclerosis  of  the  coronary  arteries 
of  the  heart. 


CHAPTER    IX. 
GOITER  DEATH. 

In  patients  suffering  from  tracheobronchial  stenosis,  any  congestion 
of  the  respiratory  apparatus  or  any  physical  exertion  increases  the  short- 
ness of  breath;  even  talking  taxes  their  strength  to  the  utmost,  and  it  is 
not  unusual  for  them  to  stop  in  the  middle  of  a  sentence  to  get  breath: 
inspiratory  stridor  is  then  more  or  less  always  present.  With  a  little 
care,  however,  such  patients  may  get  along  for  years  without  choking 
spells,  inasmuch  as  they  adapt  themselves  to  the  smaller  caliber  of  the 
trachea  and  to  the  diminished  oxygenation  of  the  blood;  yet,  disregard- 
ing the  fact  that  such  patients  are  more  liable  than  others  to  have 
pneumonia,  their  lives  are  otherwise  always  endangered  because  a  slight 
catarrh,  or  any  other  trifling  cause,  may  determine  a  dangerous  choking 
spell  which  may  terminate  in  death. 

Sudden  death  is  one  of  the  most  tragic  and  often  one  of  the  most 
unexpected  endings  of  those  afflicted  with  goiter,  especially  with  the 
intrathoracic  variety. 

One  who  has  seen  many  goiter  patients  with  choking  spells  knows, 
for  instance,  that  these  patients  learn  by  experience  that  twisting  of 
the  head  in  certain  ways  increases  dyspnea,  whereas  earning  the  head 
in  some  definite  manner  makes  respiration  easier,  because  in  so  doing 
they  unconsciously  relax  certain  muscles,  thus  diminishing  the  direct 
pressure  upon  the  goiter,  which  in  turn  allows  respiration  to  take  place 
more  freely.  If,  however,  during  sleep  they  should  make  a  false  move- 
ment of  the  head  so  as  to  twist  or  compress  the  trachea,  the}'  at  once 
awaken  in  need  of  air  and  try  to  find  again  the  stereotyped  position  in 
which  respiration  is  easier,  and  which  Rose  calls  "  Die  letzte  Stellung." 
If  they  succeed,  all  well  and  good:  the  spell  will  soon  be  over.  But  if 
they  do  not,  and  if  there  is  at  the  same  time  a  congestion  of  the  larynx 
and  a  catarrhal  condition  of  the  windpipe,  and  if  there  is  added  to  this 
as  the  consequence  of  congestion  an  active  and  passive  venous  stasis 
in  the  goiter,  which  results  in  an  increased  volume  of  the  goiter  itself, 
and  in  turn  in  an  increased  pressure  on  the  windpipe,  then  the  efforts 
of  the  patient  to  get  his  breath  are  useless:  the  tracheal  stenosis  has 
become  complete  and  death  must  ensue. 

As  said  before,  these  choking  spells  and  this  type  of  goiter  occur 
most  frequently  with  the  forms  of  intrathoracic  goiter,  among  which 
the  plunging  goiter  must  be  given  due  consideration.     As  we  know,  this 


GOITER  DEATH  161 

goiter  has  a  long  pedicle,  and  has  a  wide  range  of  excursion,  since  it 
can  wander  from  the  cervical  region  into  the  mediastinal  space,  and 
vice  versa.  Suppose,  now,  that  a  sudden  hemorrhage,  or  that  an  active 
or  passive  venous  congestion  takes  place  in  that  goiter,  then  at  once  the 
latter  increases  in  size,  and  on  that  account  can  no  longer  escape  the 
superior  opening  of  the  thorax:  it  becomes  incarcerated  behind  the  ster- 
num. The  tighter  the  incarceration  the  more  marked  are  the  congestive 
symptoms,  hence  the  increased  pressure  upon  the  windpipe,  hence  suffo- 
cation and  death.  In  fact,  any  sudden  increase  in  the  volume  of  any 
form  of  goiter  is  liable  to  cause  sudden  death.  In  pregnant  women 
during  deliver}"  the  violent  efforts  of  expulsion  cause  an  intense  swell- 
ing of  the  goiter,  wrhich  in  turn  compresses  the  windpipe.  The  same  is 
true  of  sudden  hemorrhages  or  acute  infections  taking  place  in  colloid 
or  cystic  goiters.  The  same  is  true,  too,  of  these  intense  venous  conges- 
tions occurring  in  goiters  of  newborn  babies.  All  these  deaths  occur 
by  the  same  mechanism,  namely,  by  the  compression  of  the  windpipe. 
This  process  is  made  worse  by  the  spasmodic  contraction  of  the  cervi- 
cal muscular  belt,  especially  that  of  the  sternocleidomastoid  muscles 
acting  as  auxiliary  muscles  of  respiration  during  the  dyspneic  spell.  In 
such  conditions  the  goiter  plays  the  part  of  a  hard  ball  pressed  violently 
against  the  trachea.  This  is  especially  true  in  cases  in  wThich  the  cervical 
musculature  has  not  yet  undergone  atrophy. 

In  some  cases  pressure  on  the  windpipe  and  on  the  venous  trunks  is 
only  moderate;  the  laryngotracheal  catarrh  is  not  marked;  the  inferior 
laryngeal  nerves  are  not  traumatized,  yet  during  menstruation,  preg- 
nancy, physical  effort,  or  on  account  of  an  increase  in  the  volume 
of  a  goiter  due  to  hemorrhage  or  infection,  a  brusque  hyperemia  and 
congestion  of  the  laryngeal  mucous  membrane  takes  place  and  an 
edema  of  the  glottis  follows.  The  patient  becomes  cyanotic  and  fights  for 
air;  this  suffocating  spell  may  soon  be  over  or  may  terminate  in  death. 
This  form  of  sudden  death  has  been  especially  observed  in  pregnant 
women,  and  very  likely  because  the  renal  filter  in  pregnancy  is  often  at 
fault. 

But  there  are  cases  of  sudden  death  in  which  there  is  no  compres- 
sion at  all,  where  there  is  no  softening  of  the  windpipe,  where  the  bron- 
chial or  tracheal  catarrh  is  absent,  where  the  renal  function  is  normal, 
and  where  the  cervical  muscular  belt  has  no  murderous  intentions,  yet 
the  patient  dies  suddenly  of  suffocation.  "This  acute  choking  spell 
without  any  tracheal  stenosis  surprises  the  patient,"  says  Kronlem, 
"without  warning,  like  a  thief  in  the  night."  The  patient  may  previ- 
ously have  had  a  slight  shortness  of  breath  or  may  have  been  entirely 
well;  his  voice  may  have  been  entirely  clear;  he  may  have  been  sleeping 
quietly,  when  suddenly  he  wakes  and  rushes  to  the  window  to  get  fresh 
11 


162  GOITER  DEATH 

air.  He  can  scarcely  speak,  and  a  long  whistling  stridor  shows  that  the 
patient  is  in  danger  of  choking.  From  this  spell  he  may  recover  in  a 
short  time,  or  he  may  not. 

In  such  conditions  death  is  due  to  the  spasmodic  contraction  of  the 
glottis,  through  stretching  of  or  pressure  on  the  inferior  laryngeal  nerve  by 
the  goiter.  As  Kraus  and  Krishaber  have  shown,  the  choking  spell  due 
to  compression  of  the  inferior  laryngeal  nerve  is  not  at  all  caused  by 
paralysis  of  the  nerve  but  by  its  excitation.  When  the  nerve  is  paralyzed 
there  is  no  longer  danger  of  glottic  spasm.  Indeed,  we  know  that  the 
dilatators  as  well  as  the  constrictor  muscles  of  the  glottis  are  all  sup- 
plied by  the  inferior  laryngeal  nerve.  But  we  must  remember,  too,  that 
the  constrictors,  being  stronger  than  the  dilatators  when  irritation  of  the 
recurrent  nerve  following  pressure  takes  place,  closure  instead  of  dila- 
tation of  the  glottis  occurs:  hence  spasm  of  the  glottis.  And  let  us  not 
forget  that  pressure  on  the  inferior  laryngeal  nerve  does  not  need  to  be 
bilateral  in  order  to  cause  this  spasmodic  condition,  because  the  aryten- 
oid muscle  is  an  unpaired  muscle.  As  Dieulafoy  rightfully  says,  "This 
muscle,  which  arises  from  the  posterior  surface  and  outer  border  of  one 
arytenoid  cartilage  and  is  inserted  into  the  corresponding  parts  of  the 
opposite  cartilage,  always  has  the  same  effect,  namely,  that  of  bringing 
its  two  insertions  together  when  it  contracts,  thus  closing  the  glottis." 
It  is  the  only  muscle  in  the  organism  which  exerts  its  action  simul- 
taneously on  both  sides  of  a  symmetrical  organ.  Accordingly,  excita- 
tion of  one  of  the  recurrent  nerves  will  determine,  on  the  one  hand, 
constriction  of  the  interligamentous  glottis  by  the  action  of  the  lateral 
crico-arytenoid  muscles  and  of  the  thyro-arytenoid  muscle  on  the  corre- 
sponding side,  and  on  the  other  hand,  the  complete  occlusion  of  the 
respiratory  glottis  by  the  bilateral  action  of  the  arytenoid  muscle. 
Respiratory  and  vocal  troubles  result  from  this  combined  action. 

There  are,  however,  cases  of  goiter  death  in  which  the  laryngoscope 
shows  an  absolutely  normal  function  of  the  vocal  cords;  the  voice  is 
normal;  there  is  no  sabre-sheathed  trachea;  compression  of  the  wind- 
pipe is  only  moderate;  symptoms  of  bronchial  catarrh  are  lacking,  and 
no  plunging  goiter  can  be  incriminated,  yet  the  patient  suddenly  drops 
dead  without  a  sign  of  warning.  Death  occurs  without  a  struggle. 
This  is  the  "  Tod  ohne  kampf  of  the  Germans  and  "la  mort  sans 
phrases"  of  the  French.  In  such  conditions  death  is  absolutely  unex- 
pected; the  patient,  while  talking,  reading,  or  drinking,  suddenly  dies. 
It  is  a  goiter-heart  death;  the  heart  simply  stops.  Of  course  tracheotomy 
is  useless  and  medicine  is  powerless  in  the  presence  of  such  a  tragedy. 
The  postmortem  will  show  a  dilatation  of  the  right  ventricle,  and  dila- 
tation and  hypertrophy  of  the  left  ventricle,  fatty  degeneration  of  the 
cardiac  musculature,  brown  atrophy,  and  myocarditis.  These  are  the 
causes  of  death. 


CHAPTER   X 


CIRCULAR  GOITER. 


The  circular  goiter  is  a  goiter  which  surrounds  more  or  less  com- 
plete!}' the  trachea,  or  both  the  trachea  and  esophagus  (Figs.  49  and  50). 
The  inner  portions  of  both  lobes  of  the  thyroid  gland  grow  graduallv 
inwardly  until  they  come  in  contact,  one  with  the  other,  thus  forming  a 
ring  of  glandular  tissue  in  which  the 
esophagus  and  trachea  are  caught 
(Fig.  51).  Such  goiters  are  found  in 
the  newborn  as  well  as  in  adults,  and 
are  mostly  of  parenchymatous  nature. 

Symptoms. — Among  the  most  strik- 
ing symptoms  caused  by  a  circular 
goiter  are  dyspnea  and  dysphagia.  On 
account  of  its  anatomical  relations, 
this  form  of  goiter  is  easily  liable  to 
cause  disturbances  of  the  inferior  laryn- 
geal nerves.  It  also  frequently  causes 
sudden  death.  Circular  goiter  does  not 
need  to  be  very  large  to  cause  dyspneic 
symptoms.  In  1854  Maurer  reported 
a  case  of  a  child  who  was  suffering 
from  dyspnea.  Examination  of  the 
neck  did  not  present  anything  abnor- 
mal, yet  the  postmortem  revealed  a 
small,  circular  goiter  encircling  the 
trachea.  While  demonstrating  anatomy 
at  the  Ohio  State  Medical  College  in 
191  5,  I  found  a  most  striking  example 

of  circular  parenchymatous  goiter.  The  gland  in  toto  was  scarcely 
more  than  twice  its  normal  size.  From  the  inner  and  posterior  angle 
of  each  lobe  there  sprang  at  sharp  angles  laminae  of  thyroid  tissue 
which  passed  behind  the  esophagus,  and  came  in  contact  with  each 
other.  I  was  unable  to  ascertain  if  during  the  life  of  the  patient 
symptoms   wire    present. 

Diagnosis.  Diagnosis  is  not  always  easy.  When  a  parenchymatous 
goiter  of  moderate  size  causes  dyspneic  symptoms  which  seem  to  be 
out  of  proportion  to  the  size  of  the  goiter,  and  especially   when  one  <>i 


^■I^KS^fc. 

^^^m^^^M^^^H^^p^^^^ 

Id         \                ^^v 

m 

^  / 

Fig.  49. — Congenital  goiter.     Natural 
size.     Anterior  view. 


104 


CIRCULAR  GOITER 


both   inferior  laryngeal   nerves   are   involved,   the   possibility   of  a   cir- 
cular goiter   should   never   be   overlooked.     Palpation  may  convey  the 


Ton  que. 


Esopna^us 


Goiter 


Trachea 


Fig.  50. — Circular  goiter  surrounding  the  trachea  and   esophagus.     Autopsy  of  a  new- 
born.    Natural  size.     Posterior  view. 


impression  that  the  lobes  of  the  thyroid  seem  to  disappear  behind  the 
esophagus  and  windpipe.  Laryngoscopy,  tracheoscopy,  and  esophagos- 
copy  may  reveal  a  circular  compression  of  the  esophagus  and  windpipe. 


Fig.  51. — Pressure  upon  windpipe  and  esophagus  by  a  circular  goiter. 

Treatment. — The  treatment  of  circular  goiter  must  be  surgical.    Great 
care  should  be  taken  to  avoid  injuring  the  inferior  laryngeal  nerves. 


INTRATRACHEAL  GOITER  165 

RETROTRACHEAL  OR  RETRO-ESOPHAGEAL  GOITER. 

This  variety  of  goiter  is  developed  at  the  cost  of  an  accessory  thy- 
roid nodule,  and  is  located  behind  the  esophagus  or  windpipe.  It  is 
entirely  independent  of  the  main  body  of  the  thyroid.  This  form  of 
goiter  is  rare  and  the  main  symptoms  which  it  causes  are  dyspnea  and 
dysphagia. 

INTRATRACHEAL    GOITER. 

Intratracheal  goiter  is  very  uncommon.  With  this,  too,  women  are 
much  oftener  afflicted  than  men,  and  every  recorded  case  has  occurred 
between  the  ages  of  twelve  and  thirty-five  years.  The  only  symptom 
which  brings  the  patient  to  the  physician  is  an  increasing  dyspnea  which 
may  develop  quite  rapidly  in  a  few  weeks  or  may  take  a  slower  course. 

Laryngoscopy  and  bronchoscopy  are  the  only  two  means  of  making 
a  correct  diagnosis.  A  subglottic  tumor  will  be  seen  filling,  to  a  more  or 
less  extent,  the  lumen  of  the  trachea.  It  may  be  round,  cylindrical,  or 
oval  in  shape,  with  smooth  surface,  and  covered  by  an  intact  mucous 
membrane.  It  is  implanted  by  a  broad  basis  on  the  tracheal  wall.  Its 
average  size  is  about  2.5  cms.  in  length  to  1.5  cms.  in  thickness,  and  it 
is  nearly  always  located  in  the  upper  part  of  the  trachea  between  the 
cricoid  cartilage  and  the  first  five  tracheal  rings.  Radestock,  however, 
reported  a  case  in  which  postmortem  showed  the  tumor  located  at  the 
mouth  of  the  right  bronchus.  Intratracheal  goiter  does  not  seem  to 
show  predilection  for  any  special  portion  of  the  walls,  since  it  is  found 
in  the  anterior,  posterior,  and  lateral  walls  of  the  windpipe. 

Suspicion  of  an  intratracheal  goiter  will  be  aroused  when  dyspneic 
symptoms  cannot  be  accounted  for.  If,  in  a  young  individual  complain- 
ing of  dyspnea,  laryngoscopy  and  bronchoscopy  show  a  subglottic  tumor 
with  smooth  surface,  round  or  cylindrical  in  shape,  and  with  a  broad 
basis,  the  diagnosis  of  intratracheal  goiter  can  be  made  with  great 
probability.  As  said  before,  the  site  of  the  tumor  on  the  walls  of  the 
trachea  is  of  no  diagnostic  value.  Differential  diagnosis  will  have  to 
be  made  with  other  conditions  as  possibilities.  Enchondroma  is  far 
more  rare  than  intratracheal  goiter.  A  mistake  might  possibly  be  made 
with  a  sarcoma,  as  it  has,  too,  a  broad,  large  basis  and  smooth  surface, 
but  the  sarcoma  grows  very  much  more  rapidly,  and  thus  causes  more 
intense  dyspneic  symptoms  than  the  intratracheal  goiter. 

The  origin  of  such  tumors  must  be  referred  to  embryonic  residues 
included  in  the  tracheal  walls  at  the  time  of  their  development.  In  one 
instance,  however,  Paltauf  showed  microscopically  that  the  intra- 
tracheal goiter  in  his  case  undoubtedly  took  its  origin  from  a  goiter 
developed  in  the  isthmus  of  the  thyroid  gland,  and  which  had  penetrated 
through  the  tracheal  walls. 


CHAPTER   XI. 
CONGENITAL  GOITER  AND   GOITER   IN   CHILDREN. 

CONGENITAL    GOITER. 

If  systematic  examination  of  the  neck  of  all  newborn  were  made, 
certainly  many  more  congenital  goiters  would  be  detected  than  actually 
are.  Congenital  goiter  was  described  for  the  first  time  by  Fodere  in 
1796.  This  author  was  already  impressed  by  the  relation  which  existed 
between  congenital  and  parental  goiters.  Hausleutner,  in  18 10,  Martin, 
in  1840,  von  Ammon,  in  1842,  Pflug,  in  1875,  devoted  quite  a  good  deal 
of  attention  to  this  question  of  congenital  goiter  and  goiterous  ante- 
cedents, but  it  is  to  Virchow  and  Demme  that  we  owe  the  most  careful 
study  on  this  subject.  Reviewing  642  cases  of  goiter,  Demme  found 
37  congenital  goiters;  out  of  2292  goiterous  patients  Diethelin  saw  25 
congenital  goiters;  out  of  1996  goiters  Richard  found  43  cases  of  con- 
genital goiter;  and  in  1909  Thevenot  reported  133  cases  of  congenital 
goiter  taken  from  the  literature  and  from  his  own  personal  experience. 

Vascular  and  parenchymatous  goiter  are  the  two  most  frequent  varie- 
ties seen  in  the  congenital  form  of  goiter.  Colloid  goiter  is  very  much 
less  frequent.  Cystic  goiter  is  rare,  but  when  present  may  attain  enor- 
mous volume  as  in  Hecker's  case  reported  in  1868,  where  the  tumor  was 
so  enormous  that  it  prevented  the  normal  course  of  labor.  Addelmann 
and  Hubbauer  saw  a  congenital  cystic  goiter  whose  dimensions  were  1^ 
times  the  size  of  the  head  of  the  newborn.  Every  once  in  a  while  it  has 
been  found  that  the  congenital  goiter  had  undergone  sarcomatous  degen- 
eration. Many  of  the  congenital  goiters  reported  in  literature  as  being 
of  very  large  size  were,  as  a  rule,  teratomata.  Such  large  tumors  are  not 
seldom  associated  with  other  pathological  conditions  resulting  from 
malformations  or  retarded  development  as  hare-lip,  situs  inversus,  etc. 

The  etiology  of  congenital  goiter  is  the  same  as  that  of  ordinary 
goiter.  In  the  vascular  form,  however,  the  mechanical  influences  during 
labor  and  delivery  such  as  hyperextension  of  the  head  in  face  presenta- 
tion, persistent  occiput  posterior  positions,  pressure  on  the  fetus  from 
uterine  contractions,  and  prolonged  labor  and  deliveries,  intervene  to 
a  great  extent  as  adjuvant  etiological  factors  by  increasing  the  conges- 
tion of  the  thyroid  gland.  On  the  other  hand,  congenital  goiters  have 
a  great  obstetrical  interest.  Situated  between  the  chin  and  the  sternum, 
they  prevent  flexion  of  the  head  during  the  passage  of  the  fetus  through 


CONGENITAL  GOITER  167 

the  pelvic  route  and  hence  cause  face  presentation.  Sometimes,  espe- 
cially in  shoulder  or  buttock  presentations,  the  umbilical  cord  winds 
around  the  neck,  thus  increasing  the  congestion  of  the  goiter.  Finally, 
these  congestive  conditions  are  apt  to  occur  during  normal  labor  in 
conjunction  with  all  pelvic  deformities. 

Parenchymatous  goiter  is,  more  strictly  speaking,  the  true  form  of 
congenital  goiter.  The  influence  of  heredity,  especially  on  the  mother's 
side,  cannot  be  denied.  Out  of  53  congenital  goiters  Demme  found 
that  in  37  the  parents  had  goiter,  while  in  23  cases  the  mothers  alone 
were  goiterous.  Out  of  43  cases  Richard  found  22  in  which  the  mother 
had  goiter,  but  in  1  only  did  he  find  goiter  in  both  parents.  In  the 
7  cases  which  I  have  seen  and  in  the  9  cases  reported  bv  Riibsammen 
in  each  case  the  mothers  had  goiter.  Furthermore,  congenital  goiter  is 
far  more  prevalent  in  regions  where  goiter  is  endemic,  but  this  is  no 
longer  surprising  as  soon  as  we  admit  that  the  causes  which  produce  it 
are  the  same  as  the  ones  which  produce  endemic  goiter.  Syphilis  or 
tuberculosis  cannot  be  regarded  as  playing  any  part  in  the  etiologv  of 
congenital  goiter.  Commandeur  seems  to  think  that  congenital  goiter 
is  not  found  in  primiparae,  as  the  5  cases  reported  bv  him  occurred  in 
multipara.     This  statement,  however,  has  not  been  confirmed. 

Histologically  the  congenital  goiter  does  not  differ  materially  from 
the  forms  seen  in  adults  except  that  its  vascularization  mav  be  more 
intensely  developed.  Its  volume  is,  of  course,  variable,  but  seldom 
exceeds  the  size  of  an  egg.  As  a  rule  congenital  goiter  is  entirely  cer- 
vical; in  some  instances,  however,  it  has  been  found  intrathoracic. 
Congenital  goiter  may  affect  the  circular  form  (Figs.  49  and  50),  in  that 
case  it  is  most  dangerous,  as  it  may  cause  fatal  spells  of  suffocation. 

Symptoms. — Even'  congenital  goiter  does  not  necessarily  produce 
symptoms.  Many  of  these  goiters  remain  latent  and  subside  rapidly 
with  or  without  treatment.  In  other  instances,  however,  thev  grow 
and  finally  attain  a  large  size.  These  goiters,  as  a  rule,  are  not  the  dan- 
gerous ones,  because  everybody  is  aware  of  their  presence,  and  since 
their  symptoms  are  not  alarming  there  is  plenty  of  time  to  apply  medi- 
cal treatment  which,  as  a  rule,  is  thoroughly  successful.  To  be  sure, 
they  may  disturb  the  little  patient  by  their  volume,  and  they  may  cause 
dyspnea  and  dysphagia;  in  the  latter  case  the  baby  will  refuse  to  nurse. 
In  other  more  benign  forms  of  congenital  goiter,  interference  with  respi- 
ration is  only  moderate  and  causes  what  is  known  as  the  asthma  neona- 
torum. These  cases,  however,  properly  handled  can  be  satisfactorily 
managed. 

I  his  is  not  true  of  the  fulminating  forms  of  congenital  goiter.  Often- 
times in  that  form  of  goiter  the  little  child  is  born  dead;  if  not,  the 
accidents  develop  rapidly;  cyanosis  is  intense;  dyspnea  is  quite  marked; 


168 


CONGENITAL  GOITER  AND  GOITER  IN  CHILDREN 


stridor  with  supra-  and  infrasternal  tirage  is  present;  the  mouth  and 
trachea  are  filled  with  mucus;  the  voice  is  hoarse;  the  wailing  is  weak, 
the  cry  rasping  and  shrill;  the  eyes  are  protruding,  and  death  soon 
follows. 

Treatment  of  Congenital  Goiter. — To  a  certain  extent  the  treatment 
of  congenital  goiter  may  be  prophylactic.  For  instance,  if  to  a  goiterous 
woman  who  is  known  to  have  already  borne  goiterous  children,  thy- 
roid extract  is  administered  with  caution  during  her  pregnancy,  the 
development  of  congenital  goiter  may  be  prevented. 

When  the  swelling  is  mostly  of  congestive  nature  it  soon  retrocedes 
spontaneously;  at  any  rate,  ice  applied  over  the  region  of  the  thyroid 
will  be  beneficial.  When,  however,  the  enlargement  is  mostly  of  paren- 
chymatous nature,  and  when  the  symptoms  are  not  too  alarming,  medi- 
cal treatment  should  be  started  at  once.  The  following  lodin  ointment 
is  very  effective  and  easily  used: 


Kal.  iodat.    . 
Aq.  dest. 
Lanolin   . 
Vaseline  . 
Tinct.  of  iodin 


5-0 

IO.O 

30.0 

70.0 

10  drops. 


The  6  cases  which  I  have  seen,  and  which  were  so  treated,  responded 
beautifully  to  the  treatment.  It  goes  without  saying  that  medical 
treatment  will  have  no  effect  upon  a  cystic  goiter. 

When  the  child  is  born  in  a  state  of  apparent  death  all  the  known 
means  for  resuscitating  a  baby  should  be  employed.  Warm  baths  for 
the  lower  half  of  the  body  and  ice-water  on  the  cervical  region  may  be 
beneficial,  while,  as  in  one  instance,  the  forward  pulling  of  the  lower 
jaw  may  put  a  stop  to  suffocation.  Sometimes  by  grasping  the  thyroid 
tumor  between  the  fingers  and  pulling  it  upward  and  forward,  one  may 
be  able  to  bring  back  respiration.  In  that  case  pressure  is  due  to  incar- 
ceration of  the  goiter  at  the  superior  opening  of  the  thorax.  If  this 
maneuver  has  succeeded  the  little  patient  may  do  better  if  he  is  kept 
lying  flat  on  his  back,  with  a  pillow  under  his  shoulders  and  the  head 
in  hyperextension. 

If,  however,  everything  has  failed,  one  should  no  longer  hesitate. 
A  transverse  incision  should  be  made  over  the  tumor,  and  the  goiter 
liberated  and  resected,  unilaterally  or  bilaterally  as  the  case  may  be. 
If  hyperplasia  involves  the  isthmus  more  than  the  remainder  of  the 
gland,  isthmectomy  may  be  all  that  is  necessary.  If,  at  the  same  time, 
thymus  hyperplasia  is  present,  thymectomy  must  be  done  quickly. 

It  should  always  be  borne  in  mind  that  the  operation  is  in  itself 
dangerous,   as   the   little   patients   do   not   stand   shock  or  hemorrhage. 


GOITER  IN  CHILDREN  169 

Yet  there  is  nothing  else  to  be  done.  The  mortality  in  the  few  cases 
that  have  been  reported  varies  from  6  to  8  per  cent.  Tracheotomy  is 
more  dangerous,  and,  as  a  rule,  fatal  on  account  of  the  bronchopneumonia 
which  follows.  Furthermore,  if  we  remember  that  in  such  conditions 
the  trachea  is  covered  by  an  enlarged,  congested  isthmus,  extending 
from  the  larynx  to  the  sternum,  and  through  which  one  will  have  to  go, 
and  if  we  remember  that  below  there  are  the  thymus  and  the  innomi- 
nates,  and  that  in  children  the  windpipe  is  small,  soft  and  easily  eludes 
the  knife,  and  if,  finally,  we  remember  that  the  operation  must  be  done 
quickly,  since  the  child  is  dying,  then  anyone  will  easily  understand 
that  tracheotomy  under  such  conditions  is  one  of  the  most  difficult 
operations  a  surgeon  can  be  called  upon  to  perform. 

GOITER   IN   CHILDREN. 

Goiter  in  children  is  not  at  all  rare,  especially  in  regions  or  countries 
where  goiter  is  endemic.  As  in  adults,  so  in  children,  all  varieties  of 
goiter  are  found;  the  parenchymatous  form,  however,  is  more  fre- 
quently seen  than  any  other.  Goiter  may  be  localized  to  one  lobe  only 
or  it  may  involve  the  entire  gland.  When  nodular  the  goiter  originates 
nine  times  out  of  ten  in  the  right  inferior  pole.  The  nodules  may  be 
unique  or  multiple.     The  goiter  may  even  be  intrathoracic. 

Simple  goiter  in  children  must  not  be  considered  as  a  mere  incident. 
It  is  often  accompanied  by  a  constitutional  syndrome  showing  a  general 
depreciation  of  the  little  patient.  As  a  rule  these  children  are  below 
the  standard  of  health  and  development;  they  look  frail  and  become 
fatigued  easily.  So  far  as  treatment  is  concerned  the  same  rules  apply 
as  those  for  any  goiter  seen  in  adults. 


CHAPTER   XII. 

SIMPLE  GOITER  AND  PREGNANCY. 

During  pregnancy  the  thyroid  gland  undergoes  nearly  always  an 
increase  in  volume  which  remains  more  or  less  marked  all  through  the 
puerperal  period.  According  to  Seitz,  this  increase  in  volume  occurs  in 
65  to  90  per  cent,  of  all  cases  of  pregnancy.  Out  of  718  pregnant  women 
seen  by  Rubsammen,  89.5  per  cent,  of  the  cases  showed  a  glandular 
enlargement.  According  to  Lange,  thyroid  hyperplasia  in  pregnant 
women  was  found  in  108  out  of  133  cases,  and  when  goiter  existed  previ- 
ously it  always  increased  in  volume  during  pregnancy.  Von  Graaf  exam- 
ined 654  pregnant  women  during  the  second  half  of  their  pregnancy; 
48.7  per  cent,  of  them  showed  a  thyroid  enlargement.  The  same  author, 
examining  256  pregnant  Viennese  women,  found  that  44  per  cent,  of 
them  had  goiter.  Of  course  many  of  these  women  had  had  goiter  prior 
to  their  pregnancy.  This,  however,  does  not  disprove  anything,  since 
he  then  found  that  38.5  per  cent,  of  these  goiterous  women  showed  a 
marked  increase  in  the  volume  of  their  goiters  during  pregnancy  and 
delivery.  According  to  Freund  and  Lange,  hyperplasia  takes  place  sooner 
in  multiparae  than  in  primiparae;  it  appears  in  the  fifth  month  in  the 
former  and  in  the  sixth  month  in  the  latter.  It  begins  to  retrocede  a 
few  hours  after  delivery  and  keeps  on  decreasing  in  size  for  weeks  after. 
The  thyroid,  however,  never  returns  to  its  normal  size.  Lactation  seems 
to  be  devoid  of  any  influence  over  the  volume  of  the  thyroid. 

The  increase  in  volume  is  due  to  hypertrophy  and  hyperplasia  of 
the  parenchymatous  elements;  colloid  and  cystic  nodules,  when  present, 
are  only  slightly  involved.  According  to  Seitz,  the  increase  in  volume 
is  due  to  the  action  of  placental  products  upon  the  thyroid.  This  gland- 
ular hyperplasia  appears  to  be  intended  to  destroy  the  products  of  auto- 
intoxication and  changes  in  the  serum  caused  by  pregnancy,  and  it 
seems  that  women  who  do  not  show  any  hyperplasia  of  the  thyroid 
are  very  apt  to  have  albuminuria  and  eclampsia  afterward.  That  the 
latter  part  of  the  supposition  is  not  simply  based  on  coincidence  was 
shown  by  Lange.  Indeed,  if  in  non-pregnant  cats  one-fifth  of  the  thy- 
roid is  removed,  no  ill  effects  whatever  are  observed,  but  if  the  cats  are 
pregnant  the  same  operation  causes  at  once  albuminuria  and  nephritis. 
Thyroid  opotherapy  undertaken  in  such  animals  causes  the  symptoms 
to  retrocede  at  once.  Nicholson  obtained  the  same  results;  the  treat- 
ment with  thyroid   extract  of  four   pregnant  women  with  albuminuria 


TREATMENT  171 

and  eclampsia  gave  very  good  results.  Seitz,  Doderlein  and  others 
believe,  however,  that  eclampsia  is  of  parathyroid  origin.  Whatever 
the  cause  mav  be  we  must  admit  that  the  thyroid  hyperplasia  in  preg- 
nancy is  a  phvsiological  process,  most  likely  intended  to  deliver  the 
organism  of  waste  products  taking  their  origin  in  the  mother  and  in  the 
child.  Perhaps,  too,  this  hyperplasia  is  intended  to  counterbalance  the 
temporarily  lost  function  of  the  ovary. 

In  the  majoritv  of  cases  during  labor,  and  especially  during  deliv- 
erv,  the  goiter  increases  materially  in  size.  Sometimes  it  acquires  such 
dimensions  that  bursting  of  the  neck  seems  to  be  imminent.  Dyspnea 
and  cyanosis  are  very  marked.  It  is  seldom,  however,  that  the  dyspneic 
svmptoms  become  such  as  to  necessitate  surgical  intervention.  During 
labor  and  delivery  pains,  on  account  of  the  pressure  from  the  goiter, 
the  carotid  pulse  disappears,  as  shown  by  taking  the  pulse  at  the  tem- 
poral arterv.  Guvon  considers  this  phenomenon  as  an  attempt  of  nature 
to  regulate  the  cerebral  circulation.  In  goiters  of  long  standing  the 
goiter-heart  is  always  present  and  must  be  regarded  as  a  bad  complica- 
tion. In  other  conditions  tachycardia  may  become  a  very  troublesome 
and  alarming  symptom. 

Treatment. — In  all  pregnant  women  the  condition  of  the  thyroid 
should  receive  careful  attention.  If  this  gland  is  found  manifestly 
enlarged  or  altered,  and  if  evidence  of  thyroid  insufficiency  is  found, 
the  active  principle  of  the  gland  in  some  available  form  should  be  admin- 
istered. On  that  point  everybody  agrees.  Small  doses  should  be  given, 
and  may  be  continued  for  several  weeks  or  months. 

As  it  has  even  been  found  that  thyroid  opotherapy  started  in  the 
early  period  of  pregnancy  prevents  thyroid  hyperplasia,  and  furthermore, 
as  it  has  been  shown  experimentally  that  it  prevents  albuminuria  and 
nephritis  in  pregnant  thyroidectomized  cats,  it  might  be  worth  while 
to  undertake  a  series  of  experiments  in  order  to  find  out  if  it  would  not 
always  be  advisable  to  feed  pregnant  women  with  thyroid  extract,  in 
order,  possibly,  to  prevent  some  of  the  dreaded  complications  of  preg- 
nancy as  albuminuria,  eclampsia,  etc. 

In  every  case  of  pregnane)  complicated  with  goiter,  be  it  simple 
or  thyrotoxic,  or  both  together,  the  wishes  of  the  parents  regarding 
the  life  of  the  child  should  always  be  carefully  ascertained,  and  the 
situation  explained  to  them.  Where  children  have  been  lost  previously, 
and  the  parents  are  desirous  of  offspring,  all  possible  means  should  In- 
used  to  continue  the  pregnancy  without,  of  course,  undue  risk  to  the 
mother.  As  soon,  however,  as  pregnancy  is  terminated  the  physician  or 
obstetrician  should  consider  it  one  of  his  first  duties  to  have  the  patient 
seek  surgical  advice  and  treatment  in  order  to  remedy  permanently  the 
thyroid  condition. 


172  SIMPLE  GOITER  AND  PREGNANCY 

When  pregnancy  complicated  with  simple  goiter  only  has  reached  an 
advanced  stage  no  one  should  become  unduly  alarmed,  the  course  of  the 
pregnancy  should  be  allowed  to  go  on,  and  in  the  great  majority  of 
cases  everything  will  terminate  to  the  entire  satisfaction  of  the  patient 
as  well  as  of  the  attending  physician,  even  if  during  labor  dyspnea  and 
cyanosis  seem  to  threaten  at  first  to  become  alarming.  If,  however,  on 
account  of  that  goiter  the  patient  has  previously  lost  a  child,  and  if  the 
symptoms  have  been  such  as  to  endanger  the  life  of  the  mother,  elective 
Cesarean  section  before  labor  should  be  selected. 

In  cases  in  which,  before  labor,  the  dyspneic  symptoms  are  marked, 
and  when  there  is  congestion  of  the  cervical  region  with  "caput  medusae" 
highly  developed,  it  is  logical  to  assume  that  dyspnea  will  be  greatly 
increased  during  labor.  In  such  conditions,  elective  Cesarean  section 
can  be  made  before  the  labor  pains  have  started.  If  labor  and  dilata- 
tion are  already  far  advanced,  pituitrin,  judiciously  administered,  may 
greatly  accelerate  labor  and  shorten  its  duration.  If  dilatation  is  more 
or  less  complete,  forceps  may  be  necessary.  If  dilatation  is  not  far 
enough  advanced,  but  engagement  is  well  started,  a  vaginal  Cesarean 
section  may  save  both  mother  and  child.  As  in  these  cases  the  sole 
object  of  surgical  intervention  is  "to  do  everything  quickly,"  the  induc- 
tion of  labor  with  elastic  bags  is,  of  course,  to  be  rejected,  as  it  is  too 
slow  and  too  uncertain  a  process,  and  adds  to  the  mother's  nervous- 
ness, and,  furthermore,  exposes  her  to  rupture  of  the  uterus  in  delivering 
a  child  through  a  partially  dilated  cervix. 

Thyroidectomy  in  such  conditions  should  be  undertaken  only  as  a 
necessity,  as  the  operation  is  rendered  extremely  difficult  by  the  enor- 
mous active  and  passive  congestion  of  the  entire  cervical  region;  further- 
more, the  thyroid  during  pregnancy  is  in  a  state  of  compensatory  hyper- 
trophy, consequently,  it  is  difficult  to  judge  how  much  gland  should  be 
removed  and  how  much  should  be  left.  Thyroidectomy  will  be  a  much 
safer  process  after  the  obstetrical  period  is  over. 

Tracheotomy  must  be  considered  only  as  a  life-saving  device. 

In  all  these  cases  the  administration  of  an  anesthetic  is  a  very  seri- 
ous matter,  and  should  be  given  the  greatest  care  and  attention,  for  it 
may  prove  disastrous.  When  possible,  surgical  intervention  should  be 
done  under  local  anesthesia. 


CHAPTER   XIII. 
CLINICAL  ASPECT  OF  MALIGNANT  GOITERS. 

In  90  per  cent,  of  the  cases,  malignant  goiter  develops  in  an  already 
preexisting  goiter;  consequently  it  is  more  frequently  found  in  regions 
where  goiter  is  endemic.  A  malignant  tumor  developing  in  a  normal 
thyroid  is  rare;  it  is  nearly  always  a  tumor  of  connective-tissue  origin, 
as  sarcoma,  endothelioma,  etc. 

Malignant  degeneration  of  goiter  occurs  mostly  between  the  ages  of 
forty  and  sixty  years.  To  be  sure,  cancerous  goiters  have  been  found  in 
younger  people,  even  in  children  ten  to  twelve  years  old,  but  these  cases 
are  certainly  not  common.  If  we  glance  over  Schmidt's,  von  Straaten's, 
Carranza's,  and  Carrel's  statistics  we  find  that: 

24  occurred  from  20  to  30  years  of  age  =  5  per  cent,  of  all  malignant 

cases; 
91  occurred  from  30  to  40  years  of  age  =  19  per  cent,  of  all  malig- 
nant cases; 

219  occurred  from  40  to  60  years  of  age  =  44  per  cent,  of  all  malig- 
nant cases; 
76  occurred  after  60  years  of  age  =  16  per  cent,  of  all  malignant 
cases. 

Sarcoma  is  more  frequently  found  in  young  people,  cancer  in  old 
ones.  Malignant  goiter  is  more  frequently  found  in  women  than  in 
men,  and  occurs  mostly  at  the  menopause,  hence  the  absolute  necessity 
of  removing  any  goiter  which  begins' to  grow  at  that  time  of  life.  Infectious 
diseases  seem  to  have  a  certain  etiological  influence  on  the  development 
of  malignant  tumors  of  the  thyroid.  It  is  not  so  infrequent,  for  instance, 
to  find  that  malignant  degeneration  follows  an  acute  spell  of  grippe. 

Relations  to  Surrounding  Structures. —  In  advanced  malignant  goiters 
the  skin  is  infiltrated,  swollen,  adherent  to  the  deep  layers,  and  is  some- 
times of  a  livid  red,  while  underneath  the  veins  are  dilated,  even  throm- 
bosed. I  he  diffuse  malignant  infiltration  may  extend  to  the  neck, 
muscles,  and  other  cervical  organs. 

In  the  majority  of  cases  the  deformations  of  the  larynx  and  trachea 
found  in  malignant  goiter,  as  compression  and  deviation  (Fig.  52), 
existed  previously  and  were  started  by  the  goiter  itself.  To  be  sine,  such 
deformations  may  have  become  more  accentuated  since  the  malignani 
degeneration  of  the  goiter  occurred,  but  they  are  not  typical  of  malig- 


174 


CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 


nancy.  The  only  feature  which  is  characteristic  of  malignancy  is  the 
invasion  of  the  tracheal  walls  by  the  tumor;  in  advanced  cases  it  may 
even  perforate  them.  Of  course  this  perforation  is  facilitated  by  the 
previously  existing  atrophy  of  the  windpipe  due  to  the  pressure  from 
the  goiter  itself. 


Fig.  52. — Pressure  upon  windpipe  by  a  malignant  goiter. 


The  esophagus,  too,  becomes  involved  by  the  malignant  degenera- 
tion. It  seldom  becomes  perforated  by  the  tumor.  Compression  may 
become  so  marked  as  to  reduce  considerably  the  size  of  the  esophageal 
canal,  hence  dysphagia,  and  in  the  last  stage,  starvation. 

The  carotid  sheath  is  usually  found  adherent  to  and  choked  by  the 
tumor.  In  advanced  stages  the  malignant  infiltration  may  involve  the 
large  vessels,  erode  them,  and  cause  a  fatal  hemorrhage,  as  in  the  cases 
reported  by  Oser,  Lebert,  and  Coulon.  Such  termination,  however,  is 
exceedingly  rare.  Less  resistant  than  the  arteries,  the  veins  are  fre- 
quently invaded  by  the  malignant  tumor,  and  it  is  not  infrequent  to 


COURSE  AND  SYMPTOMS  175 

find  them  perforated  and  filled  with  cancerous  masses.  In  one  of  my 
cases  in  which  the  cancer  extended  deep  downward  into  the  mediastinal 
space,  not  onlv  the  imae  and  jugular  veins  were  thrombosed,  but  the 
carotid  and  the  vagus  were  also  involved,  so  that  dissection  was  wholly 
impossible;  veins,  arteries,  and  nerves  had  to  be  removed  with  the 
tumor.  In  another  case  I  found  the  junction  of  the  subclavian  and 
jugular  veins  completely  thrombosed  and  perforated  by  the  tumor. 

When  malignancv  has  reached  a  certain  stage,  one  or  both  inferior 
laryngeal  nerves  will  nearly  always  be  involved.  The  one  on  the  left 
side  is  more  often  involved  than  the  one  on  the  right  side.  Both  nerves 
may  be  involved  at  the  same  time.  As  told  above,  the  vagus  and  sym- 
pathetic nerves  may  become  so  embedded  in  the  tumor  that  their  removal 
with  the  tumor  is  rendered  necessary.  This  removal,  however,  does  not 
materially  influence  the  immediate  postoperative  prognosis,  especially 
when  resection  is  unilateral. 

In  cancer  the  involvement  of  the  lymph  nodes  takes  place  earl)'. 
The  ones  which  are  affected  at  first  are  the  cervical,  found  along  the 
carotid  sheath;  only  later,  the  mediastinal  lymph  glands  become 
involved.  As  a  rule  malignant  lymph  nodes  are  small,  round,  hard, 
and  form  a  chain  along  the  carotid  sheath.  In  a  later  period  they  grow 
and  fuse  together  with  the  goiter  itself.  In  some  forms  of  malignancy 
the  lymph  nodes  are  large,  soft,  and  remind  one  of  a  malignant  lympho- 
adenoma.  Involvement  of  the  lymph  nodes  in  some  forms  of  malignancy 
may  be  totally  absent. 

Course  and  Symptoms. — The  development  of  cancer  may  be  acute, 
subacute,  or  latent. 

In  the  acute  or  fulminating  form  the  development  of  the  malignant 
tumor  is  extremely  rapid.  In  three  or  four  weeks  it  may  reach  such  a 
development  so  as  to  cause  alarming  symptoms  of  suffocation,  since  the 
tissues  soon  become  caught  by  the  diffuse,  malignant  infiltration.  This 
form  of  malignant  tumor  occurs  in  young  people,  and  is  often  mistaken 
for  acute  thyroiditis.  It  is  often  impossible  to  differentiate  it  clinically 
from  woody  thyroiditis. 

In  the  latent  form  the  gland  is  hardly  modified  in  form,  size,  and  con- 
sistency, but  numerous  metastases  are  found  in  the  lungs,  bones,  etc. 
The  thyroid  origin  of  such  metastases  is  usually  discovered  at  autopsy 
or  when  the  microscopic  examination  happens  to  be  made  from  a  lump 
removed  bv  operation.    This  form  of  malignancy  is  rare. 

Usually  the  development  of  malignant  tumor  follows  the  subacute 
type.  It  occurs  in  patients  who  previously  had  goiter,  winch  may  haw- 
been  stationary  for  years.  Some  day,  however,  without  any  apparent 
cause,  it  begins  to  enlarge  and  to  grow  with  comparative  rapidity.  It 
soon    interferes  with    respiration,   the   voice   becomes    rough,    harsh    and 


176 


CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 


rapidly  bitonal;  deglutition  is  slightl)/  difficult;  shooting  pains  especially 
toward  the  ear  and  along  the  cervical  and  brachial  plexuses  are  complained 
of.  Little  by  little  the  limits  of  the  goiter  are  less  sharply  outlined; 
the  tumor  becomes  adherent  to  the  muscles  and  other  neighboring  tis- 
sues (Fig.  53)  and  grows  downward  toward  the  mediastinal  space.  The 
goiter  loses  its  previous  softness  and  becomes  hard.  This  is  a  symptom  of 
great  diagnostic  value. 

Gradually  respiration  becomes  more  difficult,  a  barking  cough  is 
frequent,  and  paroxysmal  choking  spells  soon  dominate  the  scene. 
These  suffocating  spells  are  always  horrifying  to  witness.    The  face  and 

neck  are  congested;  the  veins  are  dis- 
tended; the  eyes  protrude,  and  the 
patient  makes  desperate  efforts  to  get 
his  breath.  His  hands  massage  his 
neck  as  if  he  were  trying  to  remove 
the  pressure.  The  choking  spells  suc- 
ceed one  another,  and  gradually  the 
tracheostenosis  grows  tighter  (Fig.  52), 
the  tracheobronchial  catarrh  becomes 
more  and  more  tenacious,  and  finally 
the  end  comes. 

Percussion,  auscultation,  ;c-ray,  and 
laryngoscopic  examination  will  give 
the  same  information  as  that  of  intra- 
thoracic goiter. 

On  the  anterior  and  superior  por- 
tion of  the  thorax  when  the  malignant 
tumor  has  already  progressed  beyond 
a  certain  degree,  there  is  a  collateral 
circulation,  showing  that  the  return  flow 
of  blood  toward  the  heart  is  impaired. 
At  the  same  time  edema  of  that  entire 
region  may  be  present,  and  especially  when  the  superior  vena  cava  has 
been  involved.  Sometimes  one  may  run  across  a  cancer  of  the  thyroid 
in  which  pulsations  synchronous  with  the  heart  beat  are  distinctly 
perceived,  so  much  so  that  one  thinks  of  an  aneurysm.  This  is  due 
to  the  fact  that  the  veins  of  the  thyroid,  being  thrombosed  to  a  more 
or  less  extent,  the  return  flow  of  blood  is  greatly  impaired,  and  the 
impact  of  each  new  arterial  arrival  of  blood  is  strongly  transmitted 
through  the  congested  and  solid  tumor.  This  form  of  cancer  is  called 
aneurysmal  cancer  (Figs.   54  and  55). 

Dysphagia  is  among  the  first  symptoms  to  betray  the  presence  of 
cancer  of  the   thyroid.      Not   infrequently   this   compression   is   accom- 


Fig.    53. — Malignant    goiter    beyond 
operative  stage. 


COURSE  AXD  SYMPTOMS  177 

panied  by  spasm  of  the  esophageal  musculature.  In  such  conditions, 
the  swallowing  of  liquids,  especially  when  cold,  is  as  difficult  as  the 
deglutition  of  solid  food. 

Compression  of  the  inferior  laryngeal  nerves,  of  the  vagus  and  espe- 
cially of  the  sympathetic  is  frequently  seen  in  malignant  tumors  of  the 
thyroid.  Symptoms  caused  by  the  injury  of  each  one  of  these  nerves 
have  been  studied  when  describing  intrathoracic  goiter,  consequently, 
there  is  no  need  to  go  over  them  again.  Not  infrequently  patients 
complain  of  intense  neuralgia  in  the  arm,  fingers,  and  occipital  region 
of  the  side  corresponding  to  the  tumor.  These  shooting  pains  are  due 
to  compression  of  the  cervical  and  brachial  plexuses. 


Fig.  54. — Malignant  vascular     Fig.  55. — Two  weeks  after 
goiter.  operation. 

Metastases  must  be  carefully  looked  for;  they  may  be  found,  or  at 
least  suspected,  especially  in  the  skeleton  and  lungs. 

The  blood  formula  in  malignant  tumors  of  the  thyroid  does  not  differ 
in  any  way  from  the  one  found  in  malignant  tumors  of  other  organs. 

Symptoms  of  thyroid  insufficiency  in  connection  with  malignant 
degeneration  of  the  thyroid  are  not  so  frequent  as  one  would  expect. 
The  reason  for  this  is  mostly  because  the  entire  gland  is  seldom  involved. 
There  remains  nearly  always  enough  gland  to  meet  the  physiological 
requirements.  And  then,  too,  we  know  that  malignant  cells  of  the  thy- 
roid have  not  lost  their  physiological  properties:  they  are  still  capable 
of  normal  function. 
12 


ITS  CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 

Symptoms  of  hyperthyroidism,  as  tachycardia,  tremor,  even  exoph- 
thalmos, have  been  noticed  quite  frequently  in  connection  with 
malignant  tumors. 

Diagnosis. — When  no  tumor  is  seen  in  the  cervical  region,  diagnosis 
is  difficult.  In  that  case  all  the  symptoms  discussed  in  the  chapter  on 
Intrathoracic  Goiter  must  be  searched  for.  Diagnosis  of  a  malignant 
intrathoracic  accessory  thyroid  gland  is  seldom  thought  of.  In  differential 
diagnosis  between  tuberculous  lymph  nodes,  malignant  branchioma,  can- 
cerous lymph  glands  symptomatic  of  cancer  of  the  esophagus,  pharynx, 
or  even  stomach,  aneurysm  of  the  aorta  will  have  to  be  discussed.  Too 
often,  however,  the  true  diagnosis  becomes  patent  only  at  the  operation. 

Very  much  easier  is  the  diagnosis  of  malignant  degeneration  of  the 
thyroid  gland  when  a  tumor  is  present  in  the  cervical  region.  In  that 
case  we  have  to  deal  with  a  patient  who  has  had  a  goiter  before,  and 
which  may  not  have  given  him  any  trouble  thus  far.  Some  day,  how- 
ever, without  any  apparent  reason,  the  goiter  begins  to  grow  rapidly, 
and  soon  interferes  with  respiration  and  deglutition.  Note,  furthermore, 
that  the  patient  is  of  middle  age,  that  perhaps  it  is  a  woman  undergoing 
menopause.  Note,  too,  that  the  goiter  has  lost  its  softness,  and  has 
become  irregular  in  surface  and  peculiarly  hard  in  consistency.  This 
is  enough  to  warrant  a  diagnosis  of  malignancy.  If  we  add  to  this,  that 
the  goiter  has  lost  its  sharp  limits,  that  shooting  pains  are  present,  that 
the  inferior  laryngeal  nerve  has  become  involved,  then  the  diagnosis  of 
malignancy  becomes  more  or  less  certain. 

Rapid  increase  in  volume  of  a  goiter,  which  has  remained  inactive  for 
a  long  time,  and  changes  in  its  consistency,  are  two  excellent  signs  of 
malignant  degeneration.  What  is  true  of  the  uterus  is  true,  too,  of  the 
thyroid.  If  after  menopause  has  taken  place,  a  uterus  which  has 
remained  in  a  quiescent  state  for  some  time,  begins  without  apparent 
reason  to  bleed,  the  chances  are  great  that  we  have  to  deal  with  a  malig- 
nant degeneration  of  that  organ.  The  same  is  true  of  the  thyroid.  If  a 
goiter,  after  a  period  of  apparent  inactivity,  begins  to  grow,  we  must 
be  on  the  lookout  for  every  symptom  tending  to  betray  the  malignancy 
of  such  a  change. 

Hemorrhages  taking  place  at  different  intervals  in  a  goiter  might 
convey  the  impression  that  some  malignant  changes  are  taking  place  in 
that  goiter,  as  there,  too,  we  shall  find  a  rapid  increase  in  volume,  hard- 
ness in  consistency,  slight  diffuseness  of  its  limits,  shooting  pains,  slight 
temperature,  etc.,  but  further  development  will  very  soon  show  (in  a 
few  days)  which  one  of  the  two  conditions  (hemorrhage  or  malignancy) 
we  have  to  deal  with.  Actinomycosis,  tuberculosis,  and  syphilis  might 
cause  the  same,  but  these  conditions  are  far  more  rare  than  malignant 
degeneration.      The    woody    thyroiditis    spoken    of   in    the    chapter    on 


TREATMENT  179 

Strumitis  might  be  mistaken  for  a  malignant  degeneration,  but  the  mis- 
take will  be  only  beneficial  to  the  patient,  as  an  early  operation  may  save 
his  life. 

Differential  diagnosis  between  carcinoma  and  sarcoma  of  the  thy- 
roid is  not  always  easy.  Sarcoma,  as  a  rule,  grows  more  rapidly,  reaches 
larger  dimensions,  is  softer  and  has  a  smoother  surface  than  carcinoma. 
In  sarcoma  the  skin  is  less  adherent  and  its  limits  are  not  quite  as  diffuse 
as  in  cancer. 

Treatment. — There  is  only  one  treatment — the  knife.  All  the  other 
means  are  palliative  measures  only,  and  all  are  disappointing.  Even 
the  "knife"  does  not  always  fulfill  its  promises;  we  might  even  say  that 
it  seldom  does.  Let  us  hope,  therefore,  that  the  time  is  not  far  distant 
when  biological  chemistry  will  give  us  an  easier  and  more  effective 
measure  than  surgery,  capable  of  curing  this  terrible  disease. 

Vv  hy  is  it  that  cancer  of  the  thyroid  as  well  as  cancer  of  other  organs 
has  been  for  so  long  considered  beyond  surgical  reach  ?  Simply  because 
all  these  cases  are  operated  too  late,  hence  disastrous  immediate  results; 
hence  high  mortality.  We  have  in  late  years  learned  to  know  that 
cancer  can  be  fought  with  some  chances  of  success  if  it  is  operated  early, 
namely,  before  the  capsule  of  the  gland  has  been  invaded,  before  the 
veins  have  become  thrombosed,  and  before  the  lymphatic  glands  have 
become  involved.  When  the  neoplasm  is  so  encapsulated  that  it  has 
not  yet  spread  outside  of  its  capsule,  and  consequently,  has  not  involved 
the  neighboring  tissues,  the  chances  for  a  happy  outcome  are  good;  at 
least,  we  can  hope  that  the  patient  will  enjoy  a  comfortable  and  peace- 
ful life  for  a  year  or  two  before  any  relapse  occurs.  Even  that  gain, 
though  short,  is  it  not  worth  our  utmost  efforts  ?  Life  is  not  so  long 
after  all  that  we  should  squander  it  lavishly. 

We  can  properly  say  that  the  outcome  of  a  cancer  case  lies  within 
the  power,  not  of  the  surgeon,  but  of  the  family  physician.  He  is  the 
one  who  sees  these  cases  first;  he  is  the  one  to  treat  them  for  months 
and  months  for  simple  goiter,  before  he  realizes  that  something  very 
serious  is  undermining  his  patient.  He  is  the  one  who  should  conse- 
quently be  educated  to  know  such  conditions,  to  differentiate  them,  and 
to  make  a  very  quick  decision  when  once  his  doubts  have  been  aroused. 
Every  physician  should  always  have  in  mind  the  possibility  of  a  cancer 
in  connection  with  any  rumor.  This  possibility  should  haunt  his  brain 
in  every  case:  he  should  be  a  "cancero-maniac."  The  satisfied  and 
dangerous  optimism  which  is  too  often  found,  and  which  unfortunately 
too  frequently  finds  its  excuse  in  ignorance,  should  be  discarded  ami 
replaced  by  an  alarming  pessimism.  In  that  start'  of  mind,  the  physician 
will  be  able  to  catch  the  significance  of  any  slighr  physical  change  in  the 
tumor,  the  meaning  of  any  apparently  slighr  and   insignificant   s\  mp- 


180  CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 

torn.  Too  often,  indeed,  these  little  prodromic  symptoms  are  not  paid 
enough  attention,  yet  they  exist.  It  is  for  us  to  train  our  senses  to 
perceive  them,  and  to  utilize  them  for  early  diagnosis.  Cancer,  as  a 
rule,  does  not  appear  like  a  thunderbolt  in  a  clear  sky,  nor  does  a  vol- 
cano emit  its  devastating  lava  without  betraying  its  intentions  by  some 
previous  uneasiness,  some  premonitory,  earthly  rumbling.  To  be  sure, 
sometimes  the  early  development  of  a  cancer  is  insidious;  in  that  case 
we  are  powerless.  Then,  too,  the  patient  is  too  often  guilty  of  an  unpar- 
donable negligence  against  which  he  should  have  been  educated.  Can- 
cer is  one  of  the  few  conditions  in  which  it  is  not  necessary  to  wait  until 
diagnosis  is  certain.  Suspicion  is  enough  to  warrant  surgical  interven- 
tion. When  we  have  to  deal  with  a  patient  of  middle  age  whose  goiter, 
without  any  apparent  reason  begins  to  grow,  to  cause  some  shooting 
pains,  to  become  hard,  especially  if  this  patient  is  a  woman  about  the 
time  of  menopause,  why  wait  until  the  entire  cervical  region  has  become 
as  hard  and  rigid  as  a  board,  until  the  patient  is  choking  to  death,  in 
other  words,  why  wait  until  it  is  too  late  to  operate  ?  In  a  great  many 
such  cases  an  early  operation,  even  when  the  diagnosis  of  cancer  is  still 
uncertain,  will  strike  the  neoplasm  in  its  embryo,  so  to  speak,  and  cure 
the  patient.  Even  if  an  operation  should  be  performed  for  a  condition, 
which,  later  on,  proves  not  to  be  malignant,  no  harm  will  be  done,  as 
the  patient  will  be  relieved  of  his  goiter,  and  may  be  saved  from  a  future 
malignant  degeneration  of  that  tumor.  Expectation  and  procrastina- 
tion can  only  be  fatal.  They  allow  the  newly  starting  neoplasm  to  reach 
a  stage  beyond  which  the  words  of  Dante  sound  like  a  terrible  condem- 
nation: "Lasciate  ogni  speranza  voi  ch'  .  .  .  .  Lose  all  hope,  you 
who     .     .     .     ." 

In  operations  for  cancer  of  the  thyroid  large  incisions  must  be  used. 
The  surgeon  must  be  able  to  have  a  good  view  of  the  field,  and  an  easy 
access  to  the  organs.  There  is  no  need  to  increase  the  difficulties  of  the 
operation  by  a  narrow  incision.  Cosmetic  results  are  of  secondary 
importance. 

If  the  neoplasm  is  still  within  the  capsule  and  has  not  reached  it, 
the  operation  will  be  a  simple  one;  it  will  not  offer  more  difficulty  than 
the  ordinary  goiter.  If,  however,  the  malignant  tumor  has  invaded  the 
capsule  and  the  neighboring  tissues,  the  operation  becomes  extremely 
difficult.  It  may  necessitate  large  sacrifices,  as  the  resection  of  the 
internal  jugular  vein,  the  common  carotid,  the  sympathetic  and  vagus 
nerves.  The  windpipe  and  esophagus  may  be  so  adherent  as  to  necessi- 
tate their  partial  resection.  The  lymphatic  glands  and  the  tumor  itself 
may  extend  so  deep  behind  the  sternum  as  to  render  a  radical  operation 
impossible.  In  such  conditions  the  immediate  results  are  disastrous; 
the  mortality  is  very  high,  and,  according  to  the  statistics  of  Brown- 


TREATMENT  181 

Potter,  in  1900,  the  total  mortality  for  thyroid  operations  for  cancer 
varied  between  72  and  85  per  cent.,  according  to  the  stage  of  the  devel- 
opment of  the  cancer.  In  such  conditions  not  infrequently  relapse  of 
the  tumor  is  noticed  already  a  few  days  after  operation.  In  the  most 
favorable  cases,  however,  relapse  occurs  only  two  or  three  years  after; 
exceptionally  it  may  not  appear  at  all,  as  in  the  cases  of  Roux  and  Kopp 
in  which  relapse  had  not  occurred  six  years  after  an  operation  for  a 
cancerous  goiter  in  which  a  partial  resection  of  the  trachea  had  proved 
necessary.  In  1900  Madelung  reported  100  cases  of  malignant  tumor 
of  the  thyroid;  59  times  death  followed  the  first  month  after  operation; 
39  times  relapse  occurred  in  the  sixth  month  after  operation  while  in 
the  2  remaining  cases  death  occurred  later. 

When  the  malignant  degeneration  involves  both  lobes,  and  when  the 
necessity  of  a  complete  removal  of  the  tumor  subsists,  the  surgeon  must 
not  hesitate  to  sacrifice  the  entire  gland  regardless  of  the  myxedematous 
consequences.  Between  the  two  evils,  better  choose  the  lesser  one. 
Myxedema,  if  it  does  occur,  can  be  easily  taken  care  of  by  thyroid 
opotherapy.  On  the  other  hand,  total  thyroidectomy  does  not  neces- 
sarily expose  the  patient  to  hypothyroidism,  because  accessory  thyroid 
glands  may  be  present  which  may  be  capable  of  supplying  the  deficiency 
of  the  removed  thyroid.  Sometimes  unsuspected  metastases  may  be 
present;  we  know  that  such  metastases  are  physiologically  active,  as 
illustrated  by  the  well-known  case  of  von  Eiselsberg's. 

Concomitant  unilateral  resection  of  the  internal  jugular,  of  the 
common  carotid,  of  the  sympathetic  and  vagus  nerves,  with  the  tumor 
seems  to  be  without  importance  so  far  as  the  postoperative  course  is 
concerned. 

When  the  malignant  degeneration  has  spread  throughout  the  entire 
cervical  region,  and  when  the  cervical  organs  have  become  embedded 
in  a  hard,  diffuse,  cancerous  gangue,  no  relief  should  be  expected  from 
surgery.  The  patient  has  to  be  more  or  less  abandoned  to  his  fate;  at 
the  most,  relief  may  be  sought  through  some  palliative  treatment. 
Among  the  most  important  of  these  palliative  forms  of  treatment  are 
x-ray,  radium   and  tracheotomy. 

Tracheotomy  has  proved  extremely  disappointing,  so  much  so,  that 
there  are  surgeons  who  prefer  to  let  their  patients  die  their  own  death. 
Such  views  are  to  a  certain  extent  warranted,  because  tracheotomy  111 
such  conditions  is  an  extremely  difficult  operation.  The  veins  art- 
enlarged  and  dilated;  the  skin  is  infiltrated;  the  cancerous  mass  sur- 
rounding the  trachea  is  thick,  hard,  and  non-clastic;  the  trachea  itself 
is  compressed,  displaced,  invaded  by  the  tumor  and  rendered  hardly 
recognizable  (Fig.  52).  Add  to  this,  that  the  patient  is  choking,  that 
the  operation  must  be  done  quickly  without  anesthesia,  vou  will  then 


182  CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 

understand  why  a  surgeon  might  hesitate  before  attempting  trache- 
otomy. Such  difficulties,  however,  should  certainly  never  deter  a  sur- 
geon worthy  of  the  name,  if  the  results  expected  from  such  an  interven- 
tion are  thought  likely  to  be  satisfactory.  But  as  said  before,  results 
are  very  disappointing.  A  great  many  patients  die  during  the  operation, 
a  great  man)'  others  die  a  few  hours  after,  and  many  of  those  who  sur- 
vive, die  a  few  days  after,  either  because  compression  of  the  windpipe 
takes  place  low  in  the  thorax,  or  because  bronchitis  or  broncho- 
pneumonia follows. 

When  dysphagia  is  very  marked,  feeding  of  the  patient  must  be  done 
with  an  esophageal  canula.     Gastrostomy  may  become  necessary. 

HYPOTHYROIDISM— MYXEDEM  A. 

Synonyms. — Cachexie  pachydermique;  Cachexia  Thyroidea;  Cachexia 
Thyreopriva,  or  Strumipriva. 

In  1875  William  Gull  reported  to  the  Clinical  Society  of  London 
5  cases  of  a  disease  characterized  by  a  swelling  of  the  skin,  and  a  more  or 
less  complete  apathy  of  the  patient.  The  title  of  his  paper  was,  "A 
Cretinoid  State  Supervening  in  Adult  Life  in  Woman."  {Clinical  Society 
Transactions,  Vol.  7.) 

William  Ord,  in  1877,  published  6  other  new  cases  which  he  called 
myxedema  on  account  of  the  edematous  infiltration  of  the  skin.  Char- 
cot, in  1879,  reported  other  cases,  and  called  the  disease,  "cachexie 
pachydermique."  All  the  cases  reported  up  to  this  time  were  found  in 
women  only. 

Savage,  in  1880,  was  the  first  to  report  a  case  of  myxedema  in  the 
male.  In  the  same  year  Madden  called  attention  to  the  fact  that  in 
myxedema  an  atrophy  of  the  thyroid  gland  was  constantly  present, 
but  he  did  not  see  any  etiological  relation  between  these  two  conditions. 
He  thought  that  atrophy  was  due  to  a  vasoconstriction  of  the  gland 
itself. 

At  about  the  same  time  Kocher,  of  Berne,  and  Reverdin,  of  Geneva, 
called  attention  to  the  results  supervening  after  complete  removal  of 
the  thyroid  gland.  Kocher  gave  to  the  clinical  syndrome  resulting  from 
complete  thyroidectomy  the  name  of  Cachexia  Strumipriva;  Reverdin 
called  it  Operative  Myxedema. 

The  Kocher-Reverdin  Controversy. — The  publications  of  Kocher  and 
Reverdin,  appearing  so  nearly  at  the  same  time,  have  given  rise  to  a 
long  discussion  as  to  whom  the  priority  of  the  discovery  really  belongs. 
As  the  subject,  so  far  as  I  know,  has  never  been  threshed  out  in  Eng- 
lish medical  literature,  and  as  it  seems  only  just  to  give  to  each  the  credit 
to  which  he  is  entitled,  I  think  it  will  be  of  interest  to  go  to  the  bottom 


HYPOTHYROIDISM— MYXEDEMA  183 

of  this  controversy.     The  medical  public  shall  be  the  judge.     Here  are 
the  facts : 

i.  In  1874  Kocher  published  a  case  in  which  after  total  extir- 
pation of  the  thyroid,  psychic  and  physical  disturbances  followed.  In 
reporting  the  case  in  his  "Pathologie  et  Therapeutique  du  Goitre,"  pub- 
lished in  the  Deutsche  Zeitschrift  filr  Chirurgie,  Kocher  said,  "The  future 
will  show  if  relations  exist  between  total  extirpation  of  the  goiter  and 
the  subsequent  status  of  the  patient,  and  what  their  nature  will  be." 

2.  On  the  7th  of  September,  1882,  while  going  to  Geneva  to 
attend  the  Congress  of  Hygiene,  Kocher  happened  to  meet  Jacques  L. 
Reverdin.  Their  conversation  naturally  drifted  to  surgical  matters, 
and  among  them,  goiter  surgery.  When  asked  by  Reverdin  if  he  had 
noticed  anything  out  of  the  ordinary  after  his  goiter  operations,  Kocher 
said  that  he  had  seen  one  of  his  patients  sink  into  a  marasmic  condition 
similar  to  cretinism,  and  that  he  was  endeavoring  to  find  the  cause  of 
such  conditions,  as  it  might  prove  of  great  importance  so  far  as  surgery 
of  goiter  was  concerned. 

3.  Six  days  after  this  conversation  Reverdin  made  a  short  com- 
munication to  the  Medical  Society  of  Geneva  which  I  shall  transcribe 
in  extenso:  Out  of  14  operations  for  goiter  there  were  3  deaths,  one 
from  pneumonia,  one  from  nervous  symptoms,  and  the  third,  a  malig- 
nant goiter,  from  suffocation.  In  patients  who  recovered,  Reverdin 
noticed  two  or  three  months  after  the  operation,  weakness,  paleness, 
and  anemia;  two  of  them  showed  an  edema  of  the  face  and  hands  with- 
out albuminuria.  In  one  patient  the  pupils  were  contracted;  this  patient 
had  a  dejected  appearance,  and  his  face  became  similar  to  that  of  a 
cretin.  In  the  majority  of  patients  this  condition  took  a  long  time 
before  disappearing,  and  in  three  of  them  this  condition  was  still  present 
after  one  year.  Reverdin  mentioned  the  fact  that  nobody  had  described 
such  a  condition  before,  but  that  Kocher  a  few  days  ago  had  told  him 
that  he  had  observed  one  similar  case.  "Is  this  condition,''''  asked  Rever- 
din, "due  to  traumatism  of  the  sympathetic  nerve,  or  to  disturbances  of  the 
thyroid  gland  in  its  hematopoietic  function?"  On  account  of  such  results 
Reverdin  states  that  he  has  modified  his  technic.  He  used  to  perform 
total  thyroidectomy  when  this  was  possible;  now  he  saves  a  portion 
of  the  capsule  of  the  gland.  In  one  case  where  one  lobe  only  of 
the  thyroid  had  been  removed,  no  secondary  symptoms  followed. 

4.  On  the  \th  of  April,  1883,  Kocher  reported  the  results  of  101 
operations  for  goiter  at  the  Surgical  Congress  of  Berlin.  In  tins  com- 
munication Kocher  gave  a  masterly  description  of  a  condition  which  he 
called  cachexia  thyreopriva.  This  description  based  on  about  30  cases 
of  cachexia  thvreopn va  was  so  completely  and  so  clinically  true  that 
nothing  of  importance  has  been  added  to  it  since.     Not  only  did  Kocher 


184  CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 

give  a  full  clinical  description  of  that  condition,  but  he  also  went  a  step 
further  and  recognized  as  an  etiological  factor  of  the  disease,  total 
thyroidectomy,  and  that  physical  as  well  as  psychic  disturbances  seen 
in  patients  were  due  to  a  lack  of  thyroid  function.  With  his  marvel- 
lous and  exquisite  clinical  sense,  he  claimed  that  there  was  a  direct 
relation  between  thyroid  insufficiency,  cretinism,  and  idiocy. 

5.  On  the  15th  of  April,  1883,  namely,  11  days  after  Kocher's 
paper  at  the  Surgical  Congress  of  Berlin,  Reverdin,  in  the  Revue  Medi- 
cate de  la  Suisse  Romande,  began  the  publication  of  an  article  which 
was  continued  in  the  same  journal  on  the  15th  of  May,  1883,  and  again 
on  the  i$th  of  June,  1883.  These  publications  have  since  been  united 
in  one  fascicule  with  the  date,  "April  15th,  1883."  on  the  cover.  This 
fact  might  mislead  the  judgment  of  the  reader  who  is  not  aware  of  the 
combination  of  articles  appearing  in  three  different  successive  months 
and  given  the  date  of  the  first  article.  I  shall  summarize  these  three 
articles. 

6.  In  the  first  portion  of  the  article  in  the  Revue  Medicale  of  the 
15th  of  April,  1883,  his  first  article,  Reverdin  discusses  the  etiology  and 
symptomatology  of  goiter,  and  their  relations  to  the  neighboring  tis- 
sues. Then  follows  the  report  of  9  operations  for  goiter.  In  Case  8, 
a  few  months  after  total  thyroidectomy,  this  eminent  surgeon  noticed 
an  edema  of  the  face  and  hands,  loss  of  strength,  and  dejected  appear- 
ance. The  other  cases  in  which  total  thyroidectomy  had  been  performed, 
and  which  survived,  were  all  reported  as  being  in  excellent  condition. 
No  other  reference  to  myxedema  was  made. 

7.  In  the  Revue  Medicale  de  la  Suisse  Ro?nande  of  the  15th  of  May, 
1883,  his  second  article,  Reverdin  adds  the  report  of  13  other  cases, 
making  22  in  all,  of  goiter  operations.  In  the  foureenth  case  which 
had  undergone  total  thyroidectomy,  Reverdin  was  told  by  the  family 
that  the  patient  had  lost  strength  and  had  swollen  face  and  hands.  As 
Reverdin  saw  this  patient  only  from  afar  on  the  street,  he  could  not 
control  the  truth  of  such  statements.  However,  in  April,  1883,  when 
revising  his  cases,  Reverdin  did  see  him,  and  then  the  patient  had  com- 
pletely regained  his  health.  In  Case  16,  soon  after  total  thyroidectomy, 
tetany  occurred,  which  Reverdin  considered  as  a  symptom  of  hysterical 
origin.  (At  the  time  the  real  significance  of  tetany  was  not  known.) 
Some  time  after  the  operation  the  patient  became  afflicted  with  "troubles 
bizares."     He  gave  no  other  description  of  these  symptoms. 

Thus  out  of  22  operations,  17  were  total  extirpations;  2  deaths 
occurred;  3  cases  showed  some  peculiar  symptoms  which  we  know  now 
were  of  myxedematous  origin;  all  the  other  cases  were  reported  in 
excellent  condition. 

Summing  up  the  results  of  his  operations,  Reverdin  concluded  the 


H I  rP0  TH I  rROIDISM—M  I  'X  EDEMA  185 

article  of  May  15,  1883,  in  the  following  manner:  "Total  extirpation 
of  the  thyroid  in  goiter  presents  great  advantages.  It  prevents  relapse; 
when  the  gland  presents  several  nodules  of  colloid  or  cystic  nature,  if 
the  larger  ones  only  are  removed,  the  other  small  nodules  are  bound  to 
grow,  hence  relapse  of  goiter.  Total  extirpation  becomes  a  necessity 
when  a  diffuse,  parenchymatous  degeneration  involves  the  entire  gland. 
In  such  conditions  partial  thyroidectomy  is  not  practicable.  When  the 
entire  gland  is  pathologically  involved,  and  when  the  condition  of  the 
patient  does  not  warrant  total  extirpation  in  one  sitting,  total  extirpa- 
tion of  the  gland  must  be  made  in  two  sittings.  Another  advantage  of 
total  extirpation  is  to  leave  a  large,  clean  cavity  which  heals  up  more 
readily  than  the  one  left  by  partial  thyroidectomy.  In  the  latter  condi- 
tion mortification  of  the  glandular  tissues  left  prevents  prompt  healing. 
On  the  other  hand,  total  extirpation  is  more  dangerous  than  partial 
thyroidectomy  because  the  inferior  laryngeal  nerves  are  more  easily 
injured." 

On  page  273  of  the  same  article  of  the  1 5th  of  May,  1883,  when  speak- 
ing of  partial  extirpation  of  the  thyroid,  Reverdin  says,  "Partial  extir- 
pation of  the  thyroid  is  not  a  method  of  choice,  but  a  method  of  neces- 
sity." In  Case  19  Reverdin  decided  to  perform  a  partial  thyroidectomy 
because  of  the  condition  of  the  patient  and  says,  "One  might  be  driven 
against  his  will  to  perform  a  partial  thyroidectomy.  In  conclusion  when 
it  is  possible,  total  extirpation  is  certainly  better  so  far  as  relapse  is 
concerned;  however,  there  may  be  cases  in  which  prudence  may  oblige 
the  surgeon  to  choose  partial  thyroidectomy  before  or  even  during 
operation."  The  great  advantage  as  seen  by  Reverdin  in  partial  thy- 
roidectomy is  to  diminish  the  chances  of  injury  to  the  inferior  laryngeal 
nerves.     No  reference  whatsoever  to  myxedema. 

8.  In  the  Revue  Medicale  de  la  Suisse  Romande  of  the  15th  of 
June,  1883,  his  third  article,  Reverdin  deals  at  length  with  the  results 
of  thyroidectomies,  giving  supplementary  information  of  Cases  8,  10, 
11,  and  14,  which  are  cases  in  which  myxedematous  symptoms  occurred 
after  total  thyroidectomy.  (Why  was  such  supplementary  information 
not  given  before  with  the  report  of  the  cases,  if  such  cases  were  really 
intended  at  the  time  to  serve  as  the  clinical  working  material  from  which 
the  description  of  operative  myxedema  was  to  be  derived?)  In  the  same 
article  Reverdin  admits  having  read  the  resume  of  Kocher's  communi- 
cation to  the  Surgical  Congress  of  Berlin  on  the  4th  of  April,  [883,  and 
then  gives  a  splendid  description  of  the  condition  which  he  calls  Oper- 
ative Myxedema.  In  that  article  he  clearly  establishes  the  analogy  exist- 
ing between  spontaneous  myxedema  of  the  adult  and  that  following 
total  extirpation.  On  the  other  hand,  contrary  to  his  previous  state- 
ments, made  four  weeks  before  in  the   Revue  of  the  [5th  of  May,   1883, 


186  CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 

Reverdin  concluded  finally  that  a  partial  thyroidectomy  should  be  per- 
formed whenever  it  is  possible,  reserving  total  extirpation  of  the  thyroid 
for  cases  in  which  it  cannot  be  avoided. 

Such  are  the  facts  and  such  are  the  data  in  which  these  various  events 
occurred.     From  them  we  can  draw  the  following  conclusions: 

i.  Already  in  1874  Kocher  had  been  impressed  by  the  peculiar 
physical  and  psychic  conditions  shown  by  his  completely  thyroidec- 
tomized  patient.  He  did  not  at  the  time,  however,  recognize  their  true 
nature  and  origin. 

2.  When  Reverdin  and  Kocher  met  on  the  7th  of  September, 
1882,  and  exchanged  privately  their  views  on  goiter  surgery  and  espe- 
cially on  its  remote  consequences,  we  can  assume  from  what  both  said, 
that  each  one  of  these  illustrious  surgeons  was  becoming  aware  of  the 
fact  that  a  certain  curious  and  peculiar  condition  developed  after  opera- 
tions for  goiter,  but  neither  one  seemed  at  the  time  to  have  recognized  its 
true  significance. 

3.  The  only  official  document  on  which  Reverdin  can  possibly 
base  his  claim  to  priority  of  the  discovery  of  myxedema  is  the  short 
communication  which  he  made  to  the  Medical  Society  of  Geneva  on 
the  13th  of  September,  1882,  and  which  has  been  reviewed  above  in 
extenso.  Since  then  all  that  Reverdin  wrote  on  that  subject  was  pos- 
terior to  what  Kocher  said  on  the  \th  of  April,  1883,  at  the  Surgical  Con- 
gress of  Berlin,  and  is  consequently  of  no  avail  so  far  as  priority  is 
concerned. 

4.  In  examining  attentively  Reverdin's  report  made  at  the  Medical 
Society  of  Geneva  on  the  13th  of  September,  1882,  and  which  has 
been  transcribed  above,  we  can  draw  the  two  following  conclusions: 

(a)  The  few  remarks  made  by  Reverdin  cannot  possibly  have  the 
pretension  of  a  description  of  the  disease  as  he  mentions  only,  "the 
edema  of  the  hands  and  face  without  albuminuria,"  and  in  one  case,  the 
"cretinoid  appearance."  Others  had  called  attention  to  this  condition 
a  long  time  before  him.  Gull,  for  instance,  in  1873,  and  William  Ord,  in 
1877,  who  called  that  condition  myxedema,  and  Charcot,  in  1879,  who 
created  the  denomination  pachydermic  cachexia. 

(b)  He  did  not  see  clearly  that  thyroid  insufficiency  was  the  etiologi- 
cal factor  of  myxedema.     He  did  not  know  whether  the  gland  or  the 

sympathetic  system  was  to  blame. 

5.  After  his  report  of  September  13,  1882,  Reverdin  continued, 
nevertheless,  to  perform  total  extirpation  of  the  thyroid.  His  last  was 
performed  on  November  17,  1882,  namely,  over  nine  weeks  after  his 
communication  to  the  Medical  Society  of  Geneva.  It  is  to  be  regretted 
that  Reverdin  did  not  give  the  reports  of  all  his  cases  of  thyroid  opera- 
tions up  to  the  time  of  his  publication  on  April  15,  1883,  as  Kocher  did 


HYPOTHYROIDISM— MYXEDEM.  1  187 

up  to  April  4,  1883.  On  the  other  hand,  Kocher,  too,  performed  a 
complete  thyroidectomy  on  November  27,  1882,  and  another  one,  his 
last,  on  January  16,  1883.  From  these  facts  what  logical  conclusions 
can  we  draw?  Simply  that  at  that  time  neither  one  had  realized  the 
exact  significance  of  the  disturbances  seen  after  total  extirpation  of  the 
thyroid.  Kocher  discovered  their  real  meaning  only  when  in  January, 
February,  and  March,  1883,  he  reviewed  his  thyroidectomized  patients 
and  saw  the  results.  So  far  as  Reverdin  is  concerned,  if  he  had  discov- 
ered the  real  significance  of  total  thyroidectomy  and  its  direct  relation 
to  myxedematous  symptoms,  he  could  never  have  written  what  he  did 
in  the  Revue  Medicate  de  la  Suisse  Romande,  May  15,  1883,  namely,  that 
total  extirpation  offered  great  advantages,  and  that  partial  thyroidec- 
tomy was  not  yet  a  method  of  choice,  but  a  method  of  necessity.  (See 
above.)  Yet  four  weeks  after,  on  June  15,  1883,  in  the  Revue  Medi- 
cate de  la  Suisse  Romande,  Reverdin  says  just  the  opposite.  In  his 
judgment,  partial  thyroidectomy  should  be  given  the  preference,  and 
total  extirpation  of  the  thyroid  should  be  practised  only  when  for  some 
reasons  it  becomes  necessary.     Why  such  a  sudden  change? 

Out  of  Reverdin' s  22  thyroidectomies,  3  cases,  possibly  4,  showed 
unmistakable  myxedematous  symptoms.  All  the  other  cases  were 
reported,  in  excellent  condition.  Without  injustice  it  can  be  said  that 
there  is  certainly  a  disproportion  between  this  meager  clinical  material 
to  work  with,  and  the  splendid  clinical  description  of  operative  myxedema 
given  by  Reverdin  on  June  15,  1883. 

When  once  Kocher  became  convinced  that  myxedema  was  the  result 
of  total  extirpation,  he  remained  consistent  with  his  conclusions.  He 
never  practised  complete  thyroidectomy  again,  and  never  advocated  it 
under  any  circumstances  except  in  malignancy.  He  gave  his  masterly 
description  of  myxedema  which  holds  true  today,  and  finally  drew  up 
the  rules  which  in  thyroid  surgery  have  been  the  guide  of  each  succeed- 
ing school  of  surgeons  ever  since.  To  posterity  the  name  of  Kocher  will 
always  be  intimately  associated  with  the  thyroid  subject,  and  to  him 
belongs  the  credit  of  having,  so  to  speak,  discovered  myxedema  and 
its  true  significance.  It  would  be  unfair,  however,  not  to  give  Reverdin 
justice  and  honor,  as  he  certainly  did  suspect  a  part  of  the  truth  inde- 
pendently, and  perhaps  would  have  seen  it  all  had  he  not  been  antici- 
pated by  Kocher.  At  any  rate,  his  work,  coming  so  soon  after  the  one 
of  Kocher,  gave  Kocher's  conclusions  more  strength,  and  was  certainly 
of  great  help  in  convincing  the  surgical  public  of  the  dangers  ot  total 
thyroidectomy. 

Etiological  Relationship  between  the  Various  Forms  of  Hypothyroidism. 
—If  we  compare  the  different  forms  of  hypothyroidism,  we  shall  see 
that   there   is   between    them    an    undeniable    relationship,    and    despite 


188  CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 

the  fact  that  sometimes  notable  differences  exist  between  them,  their 
etiological  origin  is  one,  namely,  a  diminished,  or  a  suppressed  thyroid 
function.  Consequently,  these  different  forms  of  hypothyroidism  are 
only  varieties  of  the  same  disease. 

Let  us  consider,  for  instance,  operative  and  experimental  hypothyroidism. 
In  these  forms  the  thyroid  has  been  entirely  removed.  The  results  of 
this  total  thyroidectomy  in  human  beings  as  well  as  in  animals  are  the 
same:  the  metabolism  is  greatly  disturbed;  a  myxedematous  infiltration 
of  the  skin  takes  place;  the  nervous  system  is  deeply  affected,  and  the 
intelligence  is  considerably  reduced.  If  thyroidectomy  has  been  per- 
formed in  young  animals,  the  growth  of  the  skeleton  and  the  develop- 
ment of  their  central  nervous  system  are  affected.  In  short,  we  have  a 
complete  physical  as  well  as  psychic  degradation  of  the  individual. 

In  adult  hypothyroidism,  too,  the  symptoms  are  so  strikingly  similar 
to  the  ones  found  in  operative  and  experimental  myxedema  that  it  is 
impossible  not  to  see  between  them  a  close  relationship.  Since  the  cause 
of  operative  and  experimental  hypothyroidism  is  the  loss  of  the  thyroid's 
function,  the  same  etiology  is  found  in  adult  hypothyroidism;  the  differ- 
ences between  them  are  only  differences  of  degree.  In  operative  and 
experimental  hypothyroidism,  as  the  thyroid  has  been  abruptly  and  com- 
pletely surgically  suppressed,  the  clinical  symptoms  are  very  much  more 
acute  and  rapid,  whereas  in  adult  myxedema  where  the  thyroid  has 
undergone  a  slow  process  of  atrophy  and  degeneration,  the  symptoms 
are  chronic  and  slow;  ultimately,  however,  the  results  are  the  same, 
namely,  a  well-characterized  hypothyroidism.  Consequently,  from  an 
etiological  point  of  view,  operative  and  adult  hypothyroidism  can  be 
identified.  The  first  one  is  caused  by  the  sudden,  the  second,  by  the 
slow  suppression  of  the  thyroid  function. 

Suppose,  now,  that  we  go  a  step  further  and  consider  infantile  myx- 
edema. At  the  first  glance,  between  this  form  of  myxedema  and  the 
adult  one,  the  differences  are  great,  since  in  infantile  myxedema  we  have 
an  arrest  in  the  intellectual  development,  namely,  idiocy,  and  an  arrest 
of  physical  development,  namely,  nanism.  These  two  symptoms  give  to 
infantile  myxedema  a  physiognomy  of  its  own  which  is  not  found  in  adult 
myxedema.  Consequently,  at  a  superficial  survey,  these  two  diseases 
seem  to  be  entirely  different,  yet  if  we  go  back  to  what  we  see  in  experi- 
mental or  operative  myxedema  we  shall  see  that  the  relationship  between 
these  different  forms  is  a  close  one.  Hoffmeister  and  von  Eiselsberg, 
after  performing  complete  thyroidectomy  in  newborn  rabbits,  sheep,  and 
goats,  observed,  besides  the  symptoms  of  myxedema  usually  found  in 
adults,  an  arrest  of  physical  development  characterized  by  nanism  and 
an  arrest  of  intellectual  development  characterized  by  idiocy.  Complete 
thyroidectomies   performed   in   young   children   between   eight   and   ten 


HYPOTHYROIDISM— MYXEDEMA  189 

years  of  age,  as  reported  by  Bruns,  Kocher,  and  Combe,  give  the  same 
results.  Consequently,  we  must  conclude  that  these  different  forms  of 
myxedema  recognize  the  same  etiology,  and  that  the  differences  which 
exist  between  them  are  only  due  to  the  fact  that  in  children  the  loss  of 
thyroid  function  occurred  at  a  time  when  the  physical  and  intellectual 
growth  were  in  the  making:  hence,  nanism  and  idiocy.  The  sooner 
after  birth  the  loss  of  thyroid  function  takes  place  the  more  marked  will 
be  the  thyroid  insufficiency. 

What  about  endemic  cretinism?  There,  too,  as  we  shall  see  later  in 
the  etiology  of  that  disease,  the  condition  is  caused  by  thyroid  insuffi- 
ciency aggravated  by  a  noxious  condition  of  endemic  origin,  which 
most  probably  exerts  its  nocive  influence  on  the  thyroid  and  on  the  entire 
organism  not  only  during  fetal  life,  but  also  through  generations,  so  that, 
hereditarily  speaking,  that  thyroid  gland  is  normally  below  par. 

We  may  then  conclude  that  operative,  adult,  infantile  hypothyroidism 
and  cretinism  have  the  same  relationship  between  them;  they  are  only 
degrees  of  the  same  disease.  The  good  results  obtained  by  thyroid 
opotherapy  in  every  one  of  these  conditions  corroborate  these  views. 
What  is  of  importance  is  not  so  much  the  presence  or  absence  of  the 
thyroid  but  its  loss  of  function,  and  especially  the  period  of  development 
at  which  the  thyroid  ceased  to  functionate. 

Nomenclature. — The  denomination  "cachexia  thy reopriva,"  or  "cach- 
exia strumipriva,"  given  by  Kocher,  is  a  far  better  one  than  "myxe- 
dema," as  the  latter  evokes  in  the  mind  one  symptom  only,  namely,  the 
mucinoid  infiltration  of  the  skin.  It  was  adopted  at  a  time  when  noth- 
ing was  known  of  the  etiology  of  the  disease,  and  when  the  condition 
of  the  skin  was  the  most  striking  symptom  attracting  the  attention  of 
observers. 

Furthermore,  we  know  that  in  myxedema  mucinoid  infiltration  of 
the  skin  is  not  always  present.  Consequently,  this  denomination  is, 
strictly  speaking,  defective,  yet  it  has  become  so  common  in  the  medi- 
cal literature  and  has  acquired  such  a  stronghold  that  it  would  be  diffi- 
cult to  change  it.  On  the  other  hand,  if  the  denomination  "cachexia 
thyreopriva"  stands  on  a  solid  etiological  basis,  it  nevertheless  does  not 
fulfil  all  the  requirements,  as  it  applies  only  to  those  forms  of  myxedema 
where  the  gland  is  absent.  It  does  not  apply  to  these  cases  of  function- 
all)'  insufficient  thyroid  glands.  Consequently,  this  denomination,  too, 
is  insufficient. 

If  one  reads  the  medical  literature  on  myxedema,  one  cannot  but  be 
astonished  at  the  great  number  of  synonyms  invented  to  designate  the 
same  thing,  as  "cretinism,"  "idiocy,"  "idiocy  with  pachy  dermic  cach- 
exia," "cretinoid  pachydermia,"  "cretinoid  myxedema,"  "myxedema- 
tous dystrophia,"  "infantile  myxedema,"  "myxedematous  infantilism, 


190  CLINICAL  ASPECT  OF  MALIGNANT  GOITERS 

"spontaneous  infantile  pachydermic  cachexia,"  "atrophic  cretinoid 
myxedema,"  "pachydermic  cachexia,"  etc.  To  the  reader  who  is  not 
familiar  with  all  these  matters,  these  different  denominations  are  most 
confusing.  Each  one  of  these  denominations  seeks  to  set  forth  the  side 
which  struck  most  forcibly  the  mind  of  the  observer  who  invented  it, 
but  none  of  them  stands  on  a  solid  physiological  and  etiological  basis. 
It  seems  to  me  that,  as  we  know  today,  all  those  various  and  differ- 
ently designated  forms  of  diseases  have  a  common  origin,  namely, 
absence  or  insufficiency,  or  inefficiency  of  the  thyroid  function,  it  would 
be  much  more  rational,  clear,  and  simple  to  classify  them  as  follows: 

I  Surgical.  i  ._  ,      •      i 

I.  Athyroidism.  L,  •     .  I  Or  cachexia  thyreopriva. 

|  Or  cachexia  strumipriva. 

These  denominations  would  apply  to  cases  in  which  the  thyroid  has 
been  surgically  totally  removed  or  is  congenitally  absent. 


II.  Hypothyroidism. 


Surgical.  (  r    r       -i 
n  lnrantile. 

Spontaneous.  <    .  ,   . 

1  {  Adult. 

~  I  Infantile, 

rruste.    <       .  •. 
Adult. 


These  would  apply  to  cases  in  which  the  thyroid  gland,  although 
partly  or  even  entirely  present,  has  become  functionally  insufficient,  as 
after  partial  or  total  thyroidectomies,  or  where  the  thyroids  are 
degenerated,  etc. 

TTT     „      .    .    -  J  Endemic. 

111.  Cretinism.  <  r  .. 

(  Sporadic. 

By  endemic  cretinism  we  understand  the  peculiar  forms  of  thyroid 
insufficiency  found  in  connection  with  endemic  goiter.  By  sporadic 
cretinism  we  mean  that  condition  of  cretinism  which  occurs  in  regions 
where  goiter  is  not  endemic. 


CHAPTER   XI  V. 

PATHOLOGY  OF  THE  VARIOUS   FORMS   OF  THYROID 

INSUFFICIENCY. 

Thyroid. — For  a  long  time  the  etiological  relation  between  the  con- 
dition described  as  myxedema  and  the  thyroid  was  not  recognized,  but 
after  the  researches  of  Ord,  Olive,  Schiff,  Kocher,  and  Reverdin,  it 
became  known  that  an  absolutely  sine  qua  non  condition  for  the  develop- 
ment of  myxedema  was  a  lesion  of  the  thyroid.  This  is  so  true  that  the 
English  Commission  appointed  in  1884  to  study  the  etiology  of  myxe- 
dema concluded  that  the  only  lesion  which  was  constantly  found  in 
that  disease  was  thyroid  atrophy.  "Without  lesions  or  absence  of  the 
thyroid,  no  myxedema,"  says  Kocher.  Hypothyroidism  is  a  result  of 
hypofunction  of  the  thyroid  either  because  the  gland  is  partially  or 
totally  absent  or  because  it  is  degenerated.  At  any  rate,  in  hypothy- 
roidism, the  thyroid  is  never  normal. 

In  some  cases  of  congenital  athyroidism,  microscopic  examination 
shows  no  vestiges  of  the  gland  whatsoever.  In  such  cases  we  have  to 
deal  with  a  congenital  defect.  An  inflammatory  process  which  would 
have  destroyed  the  thyroid  alone  is  hardly  probable.  This  is  evidenced 
by  the  fact  that  no  traces  of  inflammation  are  discovered,  and  by  the 
fact  that  the  parathyroids  are  found  absolutely  normal.  Indeed,  if  we 
remember  how  closely  the  parathyroids  are  related  to  the  thyroid,  and 
if  we  were  to  suppose  that  athyroidism  were  due  to  an  inflammatory 
process,  then  the  small  parathyroid  bodies  would  no  doubt  show  some 
sympathetic  symptoms,  either  clinically  or  microscopically.  Such,  how- 
ever, is  not  the  case.  The  parathyroids  are  always  found  normal.  This 
fact  proves,  furthermore,  that  the  parathyroids  embryologically  develop 
independently  of  the  thyroid  gland  and  that  their  presence  does  not 
prevent  hypothyroidism  from  taking  place.  In  some  cases,  however, 
it  seems  reasonable  to  admit  that  some  toxic  infectious  influences  have 
brought  about  the  condition  of  athyroidism. 

In  the  great  majority  of  cases  of  hypothyroidism,  however,  the  thy- 
roid is  present.  A  mass  of  sclerotic  connective  tissue  takes  the  place 
of  what  was  gland  before;  it  is  hard  and  of  a  yellowish  color.  The 
epithelium  of  the  alveoli  is  degenerated,  and  a  thick  colloid  is  present. 
Von  Eiselsberg  found  in  counting  the  number  of  cells  of  the  alveoli,  that 
they  were  greatly  reduced  in  number  and  size  as  compared  to  the  cells 


192  VARIOUS  FORMS  OF  THYROID  INSUFFICIENCY 

of  normal  follicuh.  Langhans  believes  that  the  gland  has  undergone 
an  interstitial  inflammation  with  leukocyte  infiltration  and  endarteritis. 
The  process,  in  his  judgment,  resembles  the  one  seen  in  cirrhosis  of  the 
liver.  In  Stilling's  case  the  entire  gland  had  undergone  a  fatty  degen- 
eration and  was  represented  by  a  mass  of  fat;  the  thyroid  arteries  were 
not  present.  In  certain  conditions  the  connective-tissue  degeneration 
of  the  gland  is  so  thorough  that  scarcely  any  traces  of  that  organ  can 
be  found.  Such  cases  might  be  mistaken  for  congenital  athyroidism. 
Most  probably  the  cases  reported  by  Maresch,  McCollum,  and  Fabian 
belong  to  that  class.  In  cases  regarded  clinically  as  congenital  athy- 
roidism, the  presence  of  alveoli  in  the  connective  tissue  of  the  cervical 
region  have  been  detected  microscopically. 

In  many  cases  of  hypothyroidism  and  cretinism  the  thyroid,  instead 
of  being  absent  or  atrophied,  is,  on  the  contrary,  enlarged,  but  degener- 
ated. In  cretinism  we  can  say  that  in  25  per  cent,  of  the  cases  the  thy- 
roid is  absent  or  atrophied,  and  in  75  per  cent,  of  the  other  cases  the  gland 
is  enlarged  and  degenerated.  Microscopically,  the  acini  are  poorly 
developed,  the  normal  elements  of  the  gland  are  reduced  and  atrophied, 
and  an  intense  colloid  degeneration  has  taken  place.  As  a  rule,  besides 
the  degenerated  portion  of  the  gland,  other  parts  are  present  which 
appear  to  be  entirely  normal.  H.  Vogt  claims  that  a  number  of  cases  of 
cretinism  have  been  found  in  which  the  thyroid  was  absolutely  normal, 
and  Bircher,  examining  the  thyroid  glands  of  16  cretins,  found  the 
majority  of  them  mostly  normal. 

Skin. — The  infiltration  of  the  skin  with  a  mucine-like  substance  is  a 
feature  which  is  bound  to  strike  the  attention  of  the  observer.  It  is 
to  that  condition  that  the  disease  owes  its  name,  myxedema.  A  marked 
hypertrophy  of  the  connective  tissue  of  the  chorion  is  present  while  the 
sebaceous  and  sudoriparous  glands  are  atrophied.  The  connective  tis- 
sue has  an  embryonic  character;  its  fibers  are  dissociated,  forming  spaces 
in  which  a  substance  very  rich  in  mucine  is  present.  This  semifluid 
substance  filling  up  the  interstitial  spaces  gives  the  entire  skin  a  trans- 
parent appearance.  The  question  whether  this  substance  is  really  mucine 
or  not  is  not  yet  settled.  According  to  Halliburton,  the  quantity  of 
mucine  is  fifty  times  larger  than  normally.  On  the  other  hand,  Prud- 
den  in  the  majority  of  his  cases  did  not  find  mucine.  Some  authors 
seem  to  think  that  the  infiltration  of  the  skin  is  not  of  mucinoid  origin, 
but  that  it  is  due  to  an  ordinary  edema  localized  in  the  most  superficial 
layers  of  the  skin,  hence  the  reason  why  this  edema  does  not  pit  on 
pressure.  Microscopically,  the  connective  fibers  of  the  chorion  have  a 
gelatinous  aspect  and  are  swollen.  The  lymphatic  spaces  are  enlarged, 
and  the  nuclei  of  the  endothelial  walls  voluminous.  The  majority  of 
authors  consider  this  process  as  a  return  to  the  embryonic  stage.     How- 


OSSEOUS  SYSTEM 


193 


ever,  Virchow  does  not  share  this  view.  He  believes  that  instead  of 
being  regressive,  this  process  is  an  irritative  one,  similar  to  the  one 
seen  in  phlegmasia  alba  dolens,  and  elephantiasis.  It  resembles  a  granu- 
lation tissue  containing  an  increased  number  of  fibers  and  nuclei,  and 
partlv  infiltrated  with  an  amorphous  liquid  of  more  or  less  mucinoid 
appearance.  Ewald  considers  myxedema  as  a  trophic  disturbance  and 
a  degeneration  of  adipose  tissue. 

Osseous  System. — In  congenital  athyroidism  and  spontaneous  infan- 
tile hvpothvroidism  one  of  the  most  striking  pathological  findings  is 
the  retarded  growth  of  the  osseous  system.  Periosteal,  as  well  as  endo- 
chondral ossification,  is  extremely  retarded.  The  epiphyses  remain  thin 
and  cartilaginous.  Cases  have  been  seen  where  ossification  was  not 
completed  at  the  forty-fifth  year.  The  marrow  of  the  bones  shows  a 
considerable  fattv  degeneration.  These  disturbances  are  so  constant 
that  thev  may  be  considered  as  typical  of  congenital  athyroidism,  con- 
genital hypothyroidism,  and  cretinism.  The  perichondrium  as  com- 
pared to  the  normal  one  is  very  poorly  supplied  with  bloodvessels;  the 
osteoid  tissues,  too,  are  very  poorly  irrigated.  In  congenital  athyroid- 
ism and  spontaneous  infantile  hypothyroidism  the  bones  remain  so 
short  that,  after  growth  is  supposed  to  be  terminated,  the  patient  is 
and  remains  a  dwarf.  The  thickness  of  bones,  however,  is  less  affected 
than  their  length.  That  all  these  osseous  disturbances  are  due  to  the 
fact  that  the  centers  of  ossification  do  not  appear  in  due  time  is  easily 
demonstrated  by  the  x-rays.  In  a  ten-year-old  child,  for  instance,  no 
traces  of  ossification  were  found  in  the  capitulum  ossis  Hamatum,  when 
thev  should  have  been  present  normally  between  the  fourth  and  sixth 
months  after  birth.  Dieterle  has  given  a  synoptical  tableau  showing 
when  points  of  ossification  appear  normally  in  the  various  bones  of  the 
hand.     This  tableau  is  of  great  interest  and  help.     It  is  as  follows: 


./:v. 


Ossification  appears  in 


Newborn        Shaft  of  the  phalanges,  metacarpi,  radius  and  ulna 
4    months 


5 
6 

7         " 
8 

12 

i ',  years 

1  2 

2  " 
Z\        " 

A    " 

3  " 

13 


Capitatum,  I  [amatui 


Body  length. 

50  cms. 

60  cms. 


Epiphysis  of  the  radius 75  cms. 


Basilar  epiphysis  ol  the  proximal  phalanges 
Basilar  epiphysis  of  the  terminal  phalanges 

( )thcr  basilar  epiphyses 


85  cms. 

95  cms. 

ioo  cms. 


VARIOUS  FORMS  OF  THYROID  INSUFFICIENCY 

Ossification  appears  in  Body  length. 

Os  lunatum 

Multangulum  majus  and  minus 108  cms. 

Os  naviculare no  cms. 

Distal  epiphyses  of  the  ulna 117  cms. 

130  cms. 

Os  pisiforme 135  cms. 


194 

Age. 

3i  years 

4 

5 

Sh 

6 

7 
8 

9 
10 
11 
12 

13        "  Sesamoid,  hamulus  ossis  hamati 150  cms. 

16-17  years     Disparition  of  epiphyseal  lines  of  ringers  and  metacarpi  .  165  cms. 

18  years 

19  "  >  Disparition  of  all  epiphyses 170  cms. 

20  "  170-180  cms. 

Of  course  the  pathological  disturbances  in  the  skeleton  depend 
upon  the  time  of  life  in  which  the  thyroid  insufficiency  began  to  manifest 
itself;  the  sooner  after  birth  the  hypofunction  of  the  thyroid  takes  place 
the  more  marked  will  be  the  disturbances  in  the  osseous  system.  The 
pathological  changes  will  be  found  mostly  developed  in  the  bones  which 
were  still  cartilaginous  at  the  time  the  thyroid  insufficiency  started  to 
develop.  For  that  reason  the  fibrous  bones  of  the  cranium  are  the  least 
affected;  they  continue  to  grow  to  a  certain  extent  while  the  development 
of  the  other  bones  is  arrested,  hence  a  disproportion  between  the  head 
and  the  skeleton,  and  hence  a  macrocephalous  on  the  body  of  the  dwarf. 
The  growth  of  the  bones  of  the  skull,  however,  is  far  from  being  normal; 
the  large  fontanelle  remains  open  and  synostosis  of  the  cranial  bones  is 
considerably  retarded.  Kyphotic  and  scoliotic  anomalies  of  the  spinal 
column  are  quite  frequent. 

Some  authors,  as  Bourneville  and  Hertoghe,  have  claimed  that  in 
congenital  athyroidism  and  spontaneous  infantile  hypothyroidism, 
deformation  and  retarded  ossification  of  the  osseous  system  were  due 
to  rickets.  But  in  rickets  we  have  to  deal  with  an  osteoporosis  and  a 
deficient  calcification,  whereas,  in  athyroidism  and  hypothyroidism, 
simply  with  an  arrest  of  ossification.  In  rachitism  the  epiphyseal  lines, 
instead  of  being  linear,  as  in  thyroid  insufficiency,  are  irregular,  and  have 
a  "saw-tooth"  outline;  furthermore,  in  rickets  the  appearance  of  the 
points  of  ossification  is  not  retarded  as  in  hypothyroidism,  but  takes 
place  in  due  time. 

Nervous  System. — Whitewell  found  in  examining  the  brains  of  myxe- 
dematous patients  that  the  nervous  cells  were  irregular,  their  prolonga- 
tions reduced  in  number  and  their  nuclei  not  staining  as  readily  as  the 


.      GEXITAL  APPARATUS  195 

normal  ones;  vacuolization  was  present  and  neuroglia  was  increased. 
It  seems  that  these  pathological  findings  are  not  specific  for  hypothy- 
roidism inasmuch  as  they  are  also  found  in  other  pathological  conditions. 
Nowhere  in  the  central  nervous  system  can  alterations  specific  for  hypo- 
thyroidism be  found.  Stud}'  of  the  brains  of  cretins  has  not  been  done 
sufficiently  to  enable  us  to  draw  practical  conclusions  from  it.  Their 
weight  has  been  found  to  van*  between  iooo  and  1400  gms.  Micro- 
scopically, nothing  typical  has  been  found. 

Vascular  System. — Von  Eiselsberg  found  experimentally  atheroma- 
tous degeneration  of  the  bloodvessels  of  thyroidectomized  goats.  The 
same  results  have  been  found  clinically  since.  Very  advanced  athero- 
matous conditions  of  the  large  bloodvessels  have  been  reported  fre- 
quently in  very  young  myxedematous  individuals.  Even  amyloid  has 
been  found  without  apparent  cause. 

Genital  Apparatus. — -In  congenital  athyroidism,  infantile  hypothy- 
roidism, and  cretinism  the  genital  apparatus,  as  a  rule,  is  not  sufficiently 
developed;  even  if  the  cretin  reaches  an  advanced  age,  the  genital 
apparatus  remains  of  the  infantile  type.  Their  genital  capacity  is  nega- 
tive: "Nemo  dat  quod  non  habet."  These  congenital  disturbances  are, 
of  course,  in  proportion  to  the  degree  of  thyroid  insufficiency,  and  with 
the  period  of  life  in  which  such  insufficiency  has  taken  place.  In  hypo- 
thyroidism of  milder  degree  the  genital  apparatus  is  better  developed. 
Such  individuals  are  even  able  to  procreate,  although  ordinarily,  their 
offspring  come  into  this  world  cretins,  hydrocephalus,  or  dead. 

The  hypophysis  in  cretinism  and  hypothyroidism  has  been  reported 
from  various  sources  as  being  pathological.  Normally,  its  weight  varies 
between  \  and  I  gram,  consequently  all  that  is  found  above  or  below 
these  figures  may  be  considered  as  pathological.  Rogowitsch  and  others 
found  experimentally  that  the  hypophysis  after  extirpation  of  the  thy- 
roid underwent  an  hypertrophy.  This  was  regarded  by  these  authors 
as  a  vicarious  function  of  the  hypophysis  toward  the  thyroid  gland. 
Schonemann,  however,  did  not  confirm  such  views.  In  examining  112 
hypophyses  of  goiterous  individuals  he  found  that  the  hypophysis  was 
atrophied  in  direct  proportion  to  the  goiterous  degeneration  of  the  thy- 
roid gland.  On  the  other  hand,  Boyce  and  Beadles,  Bourneville  and 
Bricon,  Pisenti  and  Viola  and  Ponfick  found  that  in  cases  of  hypothy- 
roidism the  hypophysis  was  hypertrophied.  The  alterations  found  in 
the  hypophysis  involve  the  anterior  lobe  of  the  gland  only.  Abnormal 
connective-tissue  development,  fatty  or  colloid  degeneration,  necrosis 
and  Ischemia  of  the  cells,  diminution  of  then"  number,  distention  of  the 
little  gland  by  a  plasmatic  fluid,  all  these  pathological  conditions  may 
be  found  at  the  same  time,  or  separately.  Chromophil  cells  seem  to  be 
decidedly  increased  in  number,  are  enlarged,  and  remind  one  of  the  cells 
with  colloid  degeneration. 


196  VARIOUS  FORMS  OF   THYROID  INSUFFICIENCY 

The  thymus  has  up  to  this  time  not  been  paid  much  attention.  In 
a  few  cases,  however,  it  was  found  hvpertrophied,  as  in  Bayon's  case. 
On  the  other  hand,  Pineles  and  Bernheim  Kasser  reported  a  hypo- 
plasia of  the  thymus  in  cases  of  congenital  athyroidism;  in  that  case 
the  thymus  was  microscopically  free  from  lymphocytes  and  Hassal's 
corpuscles,  whereas  the  connective  tissue  was  highly  developed.  This 
might  be  considered  as  a  counter-balance  of  what  we  find  in  Basedow's 
disease,  where  the  thymus  is  hyperplastic. 

Researches  on  pancreas,  suprarenal  bodies,  and  other  glands  of 
internal  secretion  have  not  yet  been  made. 

Surgical  Athyroidism  and  Surgical  Cachexia  Strumipriva. — These 
conditions  come  on,  as  a  rule,  after  total  extirpation  of  the  gland  and  may 
appear  in  a  few  weeks,  months,  or  even  a  few  years  after  thyroidectomy. 
Young  people  are  much  more  markedly  affected  than  old  ones,  and  the 
pathological  picture  is  more  marked  in  cases  of  long  standing  than  in 
those  of  more  recent  date.  The  clinical  picture  following  total  thyroid- 
ectomy differs  according  to  the  period  of  life  in  which  the  loss  of  thyroid 
function  takes  place. 

Symptoms. — At  first  the  patient  feels  weak  and  tired.  The  lassi- 
tude following  slight  physical  exertion  is  extreme,  as  shown  for  instance, 
by  the  patient  of  Reverdin's,  who,  although  a  great  walker,  could  not, 
after  having  undergone  total  thyroidectomy,  walk  more  than  one  or  two 
miles  without  being  completely  exhausted.  Pain  and  heaviness  in  the 
limbs,  tremor  of  the  extremities,  a  sensation  of  cold  are  the  most  usual 
complaints  of  such  thyroidectomized  patients.  Their  movements  become 
slow  and  awkward;  they  lose  their  capacity  for  doing  fine  or  precise 
work;  they  lose  the  coordination  of  their  movements.  If  the  patient  is  a 
barber  he  drops  his  scissors  or  razor  unexpectedly;  if  a  seamstress,  she 
can  no  longer  do  fine  needlework,  etc.  Naturally,  this  awkwardness 
reaches  its  maximum  when  the  hands  become  edematous. 

At  the  same  time  the  intellectual  power  diminishes;  the  memory 
becomes  weak;  speech  is  difficult  or  slow;  the  patient  becomes  apathetic. 
At  first,  especially  if  it  is  a  child,  the  patient  may  try  to  conceal  his 
handicap;  as,  for  instance,  the  young  girl  spoken  of  by  Kocher,  who  in 
school  made  desperate  efforts  to  keep  up  the  pace  with  her  schoolmates. 
The  patient,  however,  soon  realizes  that  something  is  wrong  with  his 
intelligence,  and  becomes  silent,  shy,  and  self-contained. 

When  the  disease  is  well  established  the  face  is  large  and  swollen. 
The  eyelids,  especially  the  inferior  ones,  show  a  semitransparent  sacci- 
form swelling,  which  one  is  always  surprised  to  find  does  not  pit  on 
pressure.  As  these  edematous  eyelids  partially  cover  the  line  of  vision 
the  eyes  look  small  and  sunken.  The  nose  is  large;  the  lips  thick,  hang- 
ing, and  cyanotic;  the  ears  are  enlarged  and  thickened;  the  lines  of  the 


SYMPTOMS  197 

face  being  puffed,  have  lost  their  mobility  and  are  without  expression, 
and  hence  give  an  air  of  stupidity  which  recalls  cretinism.  The  skin 
of  the  hands,  feet,  and  of  the  body  gradually  becomes  swollen.  This 
edema  is  more  pronounced  in  the  morning,  and  differs  from  the  edema 
of  kidney  and  cardiac  diseases  by  the  fact  that  it  does  not  pit  on  pres- 
sure. The  skin  is  dry,  shows  a  yellowish-white,  dirty  color,  and  scales 
easily;  perspiration  is  more  or  less  suppressed;  the  hair  is  scarce;  the 
patient  "looks  old."  The  swelling  of  the  skin  extends  to  the  mucous 
membranes;  the  tongue  is  thickened;  the  patient  becomes  anemic;  the 
blood  shows  a  diminution  of  red  corpuscles,  and  a  relative  increase  of 
leukocytes;  this  leukocytosis  increases  with  the  degree  of  the  disease. 
The  pulse  is  small  and  the  heart,  as  a  rule,  shows  no  changes.  The 
temperature  is  lowered,  the  circulation,  respiration,  and  digestive  func- 
tions become  less  active.  Sensibility  to  pain  and  touch  is  diminished. 
In  short,  the  mental  as  well  as  the  physical  processes  are  considerably 
reduced,  more  or  less. 

If  total  thyroidectomy  has  been  performed  in  a  young  child,  its 
growth  stops  and  its  intellectual  faculties  regress  rapidly.  This  is  very 
well  illustrated  by  the  case  of  Dr.  Sick,  who  in  1867  performed  a  com- 
plete thyroidectomy  in  a  ten-year-old  child.  This  boy,  who  was 
extremely  intelligent,  gradually  lost  his  mental  and  intellectual  energy 
to  such  an  extent  that  when  seen  by  Bruns,  eighteen  years  after,  he  had 
the  appearance  of  a  perfect  cretin.  He  was  incapable  of  rudimentary 
work,  and  could  not  answer  the  most  elementary  questions.  His  stature 
was  the  same  as  at  the  time  of  the  operation;  his  head  only  seemed  to 
have  developed  and  was  out  of  all  proportion  to  the  rest  of  the  body. 
Kocher,  Combe,  and  others  have  reported  similar  experiences.  If  total 
thyroidectomy  is  performed  in  a  later  period  of  physical  development,  the 
symptoms  of  hypothyroidism  will  be  less  marked.  These  symptoms  pre- 
sent their  minimum  when  growth  and  sexual  development  are  terminated. 
The  condition  then  becomes  harmless,  quoad  vitam;  it  affects  only  the 
patient's  efficiency  and  often  renders  him  incapable  of  attending  to  his 
business,  thus  forcing  him  to  give  it  up,  such  as  the  barber  who  con- 
stantly dropped  his  scissors  or  razor;  the  seamstress  who  could  not 
remember  measures;  the  maid  who  dropped  everything  which  she  picked 
up,  or  the  student  who  had  become  unable  to  remember  the  simplest 
facts  of  mathematics. 

When  hypothyroidism  affects  a  severe  form  the  patient  dies  either 
from  the  condition  itself  or  from  an  intercurrent  disease.  In  other 
instances  after  a  more  or  less  prolonged  period  of  development,  hypo- 
thyroidism may  regress  spontaneously,  become  less  severe,  and  111  a  h  \\ 
instances  may  even  disappear  entirely.  Indeed  it  has  been  demon- 
strated in  a  great  main   casts  by  many  authors  that  total  extirpation  ot 


198  VARIOUS  FORMS  OF   THYROID  INSUFFICIENCY 

the  thyroid  is  not  always  followed  by  cachexia  strumipnva.  At  first 
this  seems  not  in  harmony  with  the  classical  belief  that  the  complete 
removal  of  the  thyroid  causes  hypothyroidism.  This  inconsistency, 
however,  is  only  apparent,  for  we  know  now  that  this  failure  to  follow 
the  rule  is  due  to  the  fact  that  the  gland  has  not  been  entirely  removed, 
a  small  portion  of  it  having  been  left,  as  the  processus  pyramidalis,  for 
instance.  It  may  also  be  due  to  the  presence  of  accessory  thyroid 
glands,  which  are,  as  we  know,  not  uncommonly  found  in  the  cervical 
or  mediastinal  regions;  as  soon,  however,  as  these  accessory  glands  are 
removed,  cachexia  strumipriva  follows.  Cases  of  hypothyroidism  have 
been  known  to  develop  after  the  removal  of  a  lingual  goiter. 

More  perplexing  are  the  cases  of  "partial"  thyroidectomy  followed 
by  a  well-defined  hypothyroidism.  Why  is  it  so  ?  We  must  remember 
that  certain  individuals  have  just  enough  thyroid  to  meet  the  ordinary 
physiological  demands.  They  are  constantly  verging  on  thyroid  bank- 
ruptcy. Therefore  it  will  be  easily  understood  that  the  removal  of  a 
portion  of  that  gland  puts  them  at  once  in  thyroid  physiological  inferi- 
ority. In  other  cases  postmortem  has  shown  that  after  partial  thyroid- 
ectomy the  remaining  portion  of  the  gland  has  become  atrophied  and 
invaded  by  the  connective  tissue  to  such  an  extent  that  the  glandular 
elements  have  been  partly  destroyed:  hence,  again,  producing  functional 
insufficiency.  It  goes  without  saying  that  so  far  as  thyroid  insufficiency 
is  concerned  it  does  not  matter  what  portion  of  the  gland  is  removed; 
in  ordinary  conditions,  if  any  part  of  either  of  the  two  lobes  or  isthmus, 
or  if  any  accessory  thyroid  gland  remains,  hypothyroidism  is  not  to  be 
feared. 

Spontaneous  Adult  Hypothyroidism  (Fig.  56). — This  is  eminently 
a  chronic  disease.  It  progresses  slowly  and  it  is  only  after  years  have 
elapsed  that  it  reaches  its  maximum. 

Etiology. — Excitement,  traumatic  lesions  of  the  neck,  numerous 
pregnancies,  especially  when  accompanied  with  much  loss  of  blood 
intrapartum,  tuberculosis,  alcoholism,  and  syphilis,  have  been  thought 
to  be  the  cause  of  spontaneous  adult  hypothyroidism.  Most  likely  all 
these  conditions  should  not  be  regarded  as  the  primum  movens.  They 
have  most  probably  supervened  in  conditions  of  hypothyroidism 
already  existing,  although  latent.  As  said  before,  in  certain  patients 
as  long  as  conditions  remain  normal  the  thyroid  is  barely  physiologi- 
cally sufficient;  but  as  soon  as  it  is  overtaxed  it  becomes  momentarily 
or  permanently  insufficient  to  the  task:  hence  thyroid  insufficiency. 

Spontaneous  adult  hypothyroidism  is  often  found  in  conjunction 
with  goiter  (Fig.  56).  Among  the  most  important  causes  of  spontaneous 
adult  hypothyroidism  are  acute  infectious  diseases.  This  etiological 
factor  is  being  recognized  more  and  more  every  day.     We  have  seen  in 


ETIOLOGY 


199- 


the  chapter  on  Strumitis  and  Thyroiditis  that  the  thvroid  does  not 
remain  indifferent  in  the  presence  of  acute  infectious  diseases  as  typhoid, 
malaria,  acute  inflammatory  rheumatism,  pneumonia,  etc.  It  reacts 
more  or  less  intensively,  and  in  many  instances,  may  even  reach  sup- 
puration. After  the  acute  inflammatory  stage  is  over,  the  process  is  by 
no  means  terminated.  An  insidious,  treacherous,  chronic  inflammation 
remains,  characterized  by  a  diffuse  production  of  connective  tissue 
whose  ultimate  result  is  the  destruction  of  the  secreting  epithelium  of 
the  gland,  hence  thyroid  insufficiency.  This  influence  of  infectious  dis- 
ease is  very  well  illustrated  in  one  case  reported  latelv  bv  Achard: 
myxedema  developed  in  a  child  ten  years  old  some  time  after  measles, 
and  after  forty-two  years'  duration  of  the  disease  the  patient  died. 
The  postmortem  showed  no  traces  whatsoever  of  thvroid  tissue. 


Fig.  56. — Spontaneous  adult  hypothyroidism.     The   thyroid   gland   is  barely   palpable. 


Spontaneous  adult  hypothyroidism,  although  found  everywhere,  is 
far  more  frequent  in  regions  where  goiter  is  endemic,  and  in  individuals 
whose  thyroid  is  congenitally  insufficient  on  account  of  their  goiterous 
parentage.  It  is  rare  in  the  tropics,  occurs  frequently  in  cold  climates, 
and  is  very  common  in  certain  countries,  especially  in  France  and  Swit- 
zerland. It  is  less  common  in  North  America.  Cases  of  spontaneous 
adult  hypothyroidism  have  been  reported  among  negroes. 

It  is  more  common  in  women  than  in  men.  Prudden,  in  1888,  found 
145  cases — 32  men  and  [13  women.  Heinzheimer,  in  1894,  out  of  150 
cases,  found  10  men  and  1  17  women.  (In  23  cases  the  sex  of  the  patient 
was  not  given.)  The  predisposition  of  women  to  spontaneous  adult 
hypothyroidism  is  clue  to  frequent  congestions  and  toxi-infectious  dis- 
turbances of  the  thyroid  during  sexual  life,  such  as  menstruation,  pug- 


200  VARIOUS  FORMS  OF   THYROID  INSUFFICIENCY 

nancy,  menopause.  It  is  more  common  between  the  ages  of  30  and 
50  years. 

Symptoms. — As  the  patient  has  reached  his  complete  physical  and 
mental  development  the  symptoms  found  will  correspond  to  the  ones 
seen  in  operative  myxedema  of  the  adult;  the  skeleton  is  normal,  and 
the  disturbances  of  a  psychic  order  are  not  so  marked  as  in  infantile 
hypothyroidism.  The  organs  are  not  anatomically  but  only  functionally 
disturbed. 

The  debut  of  the  disease  is  insidious,  slow,  and  progressive.  With- 
out apparent  cause,  more  often  during  the  convalescing  period  of  an 
acute  infectious  disease,  a  progressive  weakness,  physical  apathy,  and 
an  intellectual  torpor  combined  with  anemia  are  observed.  The  true 
significance  of  such  conditions,  as  a  rule,  is  not  understood  and  the 
patient  is  treated  for  anemia.  Under  medical  treatment  and  rest  these 
conditions  are  improved  or  retrocede  entirely,  but  after  a  few  weeks  or 
months  they  relapse  again,  and  then  they  follow  their  slow  but  pro- 
gressive course,  which  may  last  ten,  twenty  or  even  forty  years.  In 
the  full  development  of  the  disease  the  face  is  swollen,  the  lips  are  thick 
and  everted,  especially  the  lower  one,  and  the  nose  and  mucous  mem- 
brane of  the  nasopharynx  are  swollen,  too.  This  swelling  compels  the 
patient  to  breathe  with  open  mouth  while  sleeping,  hence  causing  loud 
snoring.  The  tongue  is  thick,  chin  plump,  and  on  account  of  the  swell- 
ing of  the  eyelids  the  eyes  seem  to  be  smaller;  the  cheeks  are  flabby  and 
the  lines  of  the  face  have  a  remarkable  immobility;  this  altogether  gives 
the  patient  an  air  of  stupidity.  His  forehead  is  often  wrinkled  and  his 
eyebrows  are  elevated  in  order  to  raise  the  swollen  lids  above  the  line 
of  vision.  In  opposition  to  what  is  seen  in  cardiac  and  renal  diseases, 
where  edema  obliterates  the  wrinkles  of  the  face,  in  myxedema  it 
exaggerates  them.  The  skin  is  yellowish  white,  waxy,  with  a  slight 
redness  on  both  malar  regions. 

The  myxedematous  infiltration  is  not  evenly  distributed  over  the 
body;  there  are  places  in  which  it  is  more  prominent  than  in  others,  for 
instance,  in  the  supraclavicular  spaces,  abdomen,  neck,  and  thorax. 
For  lack  of  perspiration  the  skin  is  dry  and  scales  off  easily.  The 
sebaceous  secretion  is  scarce  and  skin  eruptions  of  different  kinds  are 
often  present. 

The  hands  and  feet  are  thick  and  clumsy,  the  fingers  have  the  shape 
of  small,  round  sausages,  and  move  with  difficulty;  hence  the  name 
"spade-hands"  of  Gull.  The  patient  does  not  use  them  with  ease, 
hence  producing  awkwardness.  The  feet  become  deformed  and  edema- 
tous, and  the  legs  become  round  and  thick,  and  have  a  pachydermic 
appearance.  The  hair  and  eyebrows  are  thin  and  brittle,  while  in  the 
axillary  and  pubic  regions  the  hair  falls  out. 


SYMPTOMS  201 

The  symptoms  evidenced  by  the  nervous  system  are  very  striking. 
Thev  consist  in  a  weakened  memory,  slow  mental  processes,  diminution 
of  the  capacity  of  coordination,  and  diminished  activity  of  the  organs 
of  sense  and  of  the  reflexes.  The  patient  answers  questions  slowly  and 
becomes  irritable  if  pressed  with  them.  Although  he  may  usually  be 
of  a  gentle  disposition,  he  will  at  times  show  remarkable  bursts  of  rage. 
Any  mental  or  physical  exertion  is  a  burden  to  him;  his  speech  is  slow, 
but  not  stammering  or  monosyllabic.  His  slowness  is  due  to  a  slow  pro- 
cess of  ideation.  His  voice  is  more  or  less  husky  on  account  of  the 
edema  of  the  laryngeal  mucous  membrane.  The  organs  of  special  sense 
are  quite  often  affected:  hearing,  sight,  taste,  and  the  sense  of  smell 
are  diminished.  Deafness,  to  a  greater  or  less  degree,  is  common,  and 
is  not  onlv  due  to  infiltration  of  the  mucous  membrane,  but  also  seems 
to  be  of  central  origin.  Tinnitus  is  quite  frequent,  and  is  the  source  of 
much  complaint  on  the  part  of  the  patient.  The  sense  of  touch  is 
reduced  and  the  patient  is  sensitive  to  cold.  This  sensation  of  cold  is 
not  only  purely  subjective,  but  is  also  objective,  as  the  central  tempera- 
ture of  the  body  is  lowered  and  varies  between  95 °  and  97 °  F.  The 
extremities,  lips,  and  nose  are  cold  and  cyanotic;  the  circulation  is  slow 
and  the  pulse  varies  between  50  and  65.  As  a  rule  the  heart  shows  no 
abnormality. 

The  red  corpuscles  may  be  slightly  diminished,  and  the  hemoglobin 
content  reduced.  But  just  as  for  Graves'  disease,  the  most  charac- 
teristic changes  concern  the  white  cells,  so  here,  too,  as  shown  by  Kocher, 
we  find  a  leukopenia,  a  hyperlymphocytosis,  and  a  hyperpolynucleosis. 
The  coagulability  of  the  blood,  on  the  contrary,  as  shown  by  Kottmann, 
is  reduced  in  hypothyroidism,  whereas  it  is  increased  in  hyperthy- 
roidism. This  is  a  point  of  very  good  differential  diagnostic  value.  The 
urine  is  diminished  and  its  specific  gravity  varies  between  1000  and  1015. 
The  nitrogenous  exchanges  are  low.  Menstruation  when  present  may 
be  profuse  or  scarce,  but  very  often  is  suppressed.  The  patient  com- 
plains quite  often  of  rheumatic  pains  in  the  hands,  feet,  and  back. 

The  clinical  picture  of  spontaneous  adult  hypothyroidism  is  not 
always  so  complete;  many  cases  have  been  described  in  which  only  a  few 
of  the  above  symptoms  recorded  as  characteristic  of  hypothyroidism  have 
been  found.  These  cases  are  called  fruste,  larvatc,  or  incomplete  hypo- 
thyroidism. They  were  described  by  Brissaud  and  Tiberge  and  called 
by  Hertoghe,  benign  hypothyroidism.  They  art-  more  frequent  than 
one  would  expect.  We  shall  study  them  in  another  chapter.  In  senility 
the  thyroid  gland  becomes  atrophic,  undergoes  a  diffuse  sclerosis,  and 
tends  gradually  to  destroy  the  epithelial  elements  of  the  gland  itself, 
hence  hypothyroidism.  According  to  Horsley,  old  age  is  only  a  form 
of  mitigated  hypothyroidism.     He  believes  that  tin-  people  that  enjoy 


202  VARIOUS  FORAIS  OF  THYROID  INSUFFICIENCY 

a  green  old  age  owe  this  happy  condition  to  a  thyroid  which  has  remained 
normal.  The  points  of  resemblance  between  senility  and  a  slight  degree  of 
hypothyroidism  are  more  than  one.  The  changes  in  the  face,  the  falling 
out  of  the  hair,  the  dryness  of  the  skin,  the  production  of  adipose  tissue, 
the  diminution  in  the  function  of  the  nervous  system,  of  the  sensorial, 
intellectual,  and  genital  spheres,  all  these  symptoms  found  in  advanced 
old  age,  according  to  Horsley,  point  toward  a  thyroid  insufficiency  of 
moderate  degree.  In  both  cases  the  nutritional  exchanges  are  dimin- 
ished; the  pulse  is  slow;  the  temperature  is  low  and  a  sensation  of  cold 
is  present.  "The  only  differences,"  says  Ewald,  "is  that  in  old  age 
there  is  a  constant  atrophy  of  the  intestinal  tract  which  is  not  present 
in  hypothyroidism." 

It  these  views  are  correct,  thyroid  opotherapy  should  be  of  great 
value  in  preventing  old  age,  but  I  am  afraid  that  this  theory,  although 
extremely  interesting,  is  a  sister  to  the  Brown-Sequard  theory,  and 
we  know  that  the  promises  of  this  have  not  been  fulfilled.  They  who 
are  dreaming  the  dream  of  Faust  and  Ponce  de  Leon,  the  dream  of  eter- 
nal youth,  must  still  put  their  trust  in  something  else  than  in  the  feeding 
of  testicular  or  thvroid  extract. 


CHAPTER   XV. 

CONGENITAL  ATHYROIDISM,  SPONTANEOUS  INFANTILE 
HYPOTHYROIDISM,   AND   CRETINISM. 

In  this  class  we  shall  include  all  these  conditions  which  have  been 
labelled  at  various  times  as  "sporadic  cretinism,"  "congenital  or  infan- 
tile myxedema,"  "idiocy,"  "pachydermic  cachexia,"  "cretinoid  pachv- 
dermy,"  "cretinoid  idiocy,"  and  "infantile  myxidiocy." 

In  children  thyroid  insufficiency  takes  place  at  a  period  of  their 
development  when  intelligence  and  growth  are  incessantly  undergoing 
changes,  consequently,  hypothyroidism  in  children  will  differ  from  that 
of  adults.  Nanism,  or  arrest  in  the  physical  development,  and  idiocy, 
or  arrest  in  the  mental  development,  are  the  chief  differential  charac- 
teristics. Here,  too,  as  in  the  previously  described  forms  of  thyroid 
insufficiency,  all  stages  will  be  found. 

If  at  birth  the  thyroid  is  totally  absent,  nanism,  idiocy,  and  other 
hypothyroidism  symptoms  will  reach  the  maximum  of  development. 
This  is  the  congenital  form  of  athyroidism.  If  thyroid  insufficiency 
develops  at  a  later  period,  when  the  body  has  already  undergone  a  cer- 
tain evolution,  and  when  the  intelligence  has  already  awakened,  nanism 
and  idiocy  will  be  less  marked.  The  child  will  not  be  an  idiot,  but  only 
an  imbecile.  If  thyroid  insufficiency  develops  at  a  time  when  the  physi- 
cal and  intellectual  developments  have  already  reached  an  advanced 
growth  the  symptoms  will  be  less  marked,  nanism  will  be  only  sketched; 
the  intellectual  disturbances  will  be  less  noticeable,  and  then  the  little 
patient  will  not  be  called  an  idiot  nor  an  imbecile  but  simply  a  retarded 
child.  Finally,  if  the  thyroid  insufficiency  is  of  a  mild  degree  only  the 
symptoms  of  thyroid  insufficiency  will  be  benign,  too.  Let  us  call  this 
condition  fruste  infantile  hypothyroidism. 

Etiology  of  Congenital  Athyroidism  and  Spontaneous  Infantile  Hypothy- 
roidism.— In  countries  where  cretinism  is  not  endemic,  cases  of  cretin- 
ism are  found  which  resemble  closely  the  endemic  form,  yet  they  do  nor 
recognize  entirely  the  same  causes.  They  are  due  solely  to  the  absence 
of  the  thyroid  or  to  its  insufficiency.  Exogenous  influences  from  water 
and  soil  do  not  intervene  as  etiological  factors.  Such  conditions  are 
met  with  in  congenital  athyroidism  and  spontaneous  infantile  hypo- 
thyroidism. 

Congenital  athyroidism  clue  to  a  complete  absence  of  the  thyroid 
must  be  regarded   as  a   malformation;  it  is  a   congenital   delect  whose 


204 


ATHYROWISM  AND  INFANTILE  HYPOTHYROIDISM 


cause  is  still  very  obscure.  Probably,  as  in  other  forms  of  congenital 
malformations,  something  interfered  with  the  normal  development  and 
arrangement  of  embryonic  cells.  This  congenital  thyreo-aplasia  is  not 
special  to  certain  countries,  has  no  relation  whatsoever  to  endemic 
cretinism,  and  differs  from  the  endemic  hypothyroidism  by  the  fact 
that  there  is  no  endemic  goiter  or  cretinism  in  the  ascendants. 

In  spontaneous  infantile  hypothyroidism  (Fig.  57)  the  thyroid  is  always 
present;  it  may  be  either  atrophied  or  even  hypertrophied,  which  latter 
condition  occurs  very  seldom.  Hypertrophy,  however,  is  never  excessive. 
The  cause  of  that  form  of  hypothyroidism  may  be  dated  back  to  infec- 
tious diseases  of  the  mother  during  pregnancy.  We  know  that  the 
placenta  is  permeable  to  microorganisms,  therefore  it  is  logical  to  admit 

that  it  is  that  much  the  more 
easily  permeable  to  their  toxins 
which  are  liable  to  cause  an  acute 
toxic  thyroiditis  of  the  fetus  in 
utero.  Later,  this  thyroiditis  takes 
a  chronic  form,  the  thyroid  under- 
goes atrophy,  hence  a  thyroid  in- 
sufficiency after  birth. 

Tuberculosis  and  syphilis  have 
been  incriminated,  too,  as  a  caus- 
ating  factor  of  infantile  thyroid 
atrophy.  Alcoholism  of  the  mother 
during  pregnancy  has  been  found, 
too,  as  a  cause  of  thyroid  insuffi- 
ciency in  the  child.  We  know  that 
it  has  been  experimentally  demon- 
strated that  alcoholism  has  a 
damaging  influence  over  the  thyroid,  consequently  it  is  permissible 
to  assume  that  in  cases  of  severe  alcoholism  of  the  mother  during 
pregnancy,  alcoholic  intoxication  of  the  mother  may  damage  the 
thyroid  of  the  fetus  in  utero.  Severe  and  prolonged  congestions  of  the 
thyroid  due  to  dystocia  during  delivery  have  in  some  instances  been 
followed  by  thyroid  insufficiency.  Girls  are  more  often  affected  than 
boys. 

When  hypothyroidism  appears  during  the  first  years  of  infancy, 
after  the  child  has  been  seemingly  normal,  the  cause  of  such  thyroid 
insufficiency  may  be  found  in  the  acute  diseases  which  are  the  appanage 
of  childhood,  such  as  enteritis,  whooping-cough,  measles,  and  pneu- 
monia, etc. 

Cretinism. —  Etiology.  —  According  to  Kocher  the  name  "cretin" 
comes  from  the  French  word  "Chretien"  (Christian),  the  intention  being 


Fig.  57. — Spontaneous  infantile  hypo- 
thyroidism, with  some  other  polyglandular 
symptoms. 


CRETIXISM  205 

to  convey  the  idea  of  innocence  and  simple-mindedness.  Bayon  thinks 
that  the  word  "cretin"  comes  from  the  Rhaeto-Romanic  word  "cret," 
which  means  cripple,  cretin,  or  dwarf.  Others  think  that  it  is  derived 
from  the  word  "creta,"  which  means  chalk,  because  of  the  color  of  the 
skin.  The  following  anecdote  related  by  St.  Lager  might  confirm 
Kocher's  idea,  namely,  that  the  word  "cretin"  comes  from  the  French 
word  "Chretien."  "A  mayor  of  a  village  received  one  day  a  circular 
letter  asking  him  to  fill  up  an  enclosed  blank  purporting  to  establish 
the  number  of  disabled  people  of  the  town.  After  filling  the  columns 
concerning  the  blind,  the  lame,  the  hunchbacks,  the  lunatics,  etc.,  the 
mayor  stumbled  upon  the  column  'cretins.'  'Cretins?  What  is  that." 
Everybody  in  the  office  was  consulted,  but  nobody  knew  the  meaning 
of  the  word  cretin.  Finally,  the  policeman  was  sent  for  and  consulted. 
After  thinking  a  while,  'By  George,'  said  he,  'that  is  a  typographical 
error.  They  ask  you  how  many  Christians  (Chretiens)  there  are  in  your 
town.'  The  problem  was  solved.  So  the  mayor  wrote  in  the  column  of 
'cretins,'  'We  all  are.'' 

Cretinism  is  a  peculiar  clinical  form  of  thyroid  insufficiency,  and 
belongs  to  the  same  pathological  class  as  surgical,  congenital,  infantile, 
and  adult  hypothyroidism.  Many  of  the  symptoms  of  thyroid  insuffi- 
ciency seen  in  these  conditions  when  compared  with  those  seen  in  endemic 
cretinism  show  such  a  striking  similarity  that  a  parental  relation  between 
them  cannot  be  denied.  Although  in  everyone  of  these  conditions  we 
find  disturbances  of  the  skin,  of  the  osseous  system,  and  of  the  genital 
and  nervous  apparatus,  yet  a  closer  examination  shows  that  there  are 
between  them  fundamental  differences.  In  endemic  cretinism,  for 
instance,  pathological  changes  of  the  skin  are  present,  but  they  have 
not  the  same  character  as  those  seen  in  myxedema.  Scholz  says  that 
the  skin  of  the  cretin  cannot  be  even  called  "pseudomyxedematous." 
Bircher  claims  that  in  60  per  cent,  of  his  cases  of  cretinism,  myxedema 
of  the  skin  was  not  present.  Osseous  disturbances  of  the  skeleton  in 
endemic  cretinism  differ  from  those  seen  in  congenital  athyroidism.  In 
the  latter  condition  endochondral  and  periosteal  ossification  is  consid- 
erably retarded.  Ossification  in  the  epiphysis  and  synchondrosis  takes 
place  only  very  late  in  life.  The  fontanelles  remain  open  for  a  consid- 
erable period  of  time,  as  seen  in  the  postmortem  of  the  "Pacha  de 
Bicetre."  In  cretinism  the  retarded  ossification  is  very  much  more 
irregular;  only  certain  epiphyses  and  synostoses  undergo  normal  ossifi- 
cation, whereas  others  do  not.  Sometimes  we  may  see  premature  syn- 
ostosis,  hence   disproportion    between   different    parts   of    the   skeleton. 

In  endemic  cretinism  it  is  remarkable  that  the  diminution  of  cere- 
bral power  is  not  always  in  proportion  to  the  disturbances  seen  in  other 
systems  of  the  organism.      The  course  of  the  disease  is  different,  too. 


206  ATHYROIDISM  AXD  INFANTILE  HYPOTHYROIDISM 

In  endemic  cretinism,  after  a  certain  period  of  time,  the  disease  seems 
to  remain  stationary,  hence  the  long  life  of  the  cretins.  In  congenital 
athyroidism  the  disease  is  progressive  and  death  takes  place  at  a  much 
earlier  period  than  in  endemic  cretinism.  As  said  before,  no  cases  of 
congenital  athyroidism  have  been  known  to  live  longer  than  thirty 
years.  The  results  of  opotherapy  show  that  there  are  differences  between 
congenital  athyroidism,  infantile  hypothyroidism,  and  endemic  cret- 
inism. In  the  first  two  conditions  the  results  of  opotherapy  are  bril- 
liant, whereas  in  endemic  cretinism  they  are  doubtful.  Von  Wagner 
claims  that  in  endemic  cretinism  he  has  obtained  brilliant  results  with 
thyroid  opotherapy.  On  the  other  hand,  Scholz,  Kutschera,  Bircher, 
and  others  claim  that  their  results  have  been  more  or  less  negative. 

As  to  the  etiology  of  cretinism,  we  shall  see  in  studying  the  causes 
of  endemic  cretinism  and  goiter  that  there  is  a  marked  divergence  of 
opinion  among  writers.  Some,  as  Kocher,  von  Wagner,  von  Eiselsberg, 
Langhans,  and  Seigirt,  believe  that  this  endemic  cretinism  is  solely  due 
to  thyroid  disturbances.  "Without  disturbed  function  of  the  thyroid, 
no  cretinism,"  says  Kocher.  He  believes  that  the  same  noxious  causes 
producing  other  forms  of  hypothyroidism  intervene  during  fetal  life 
and  cause  cretinoid  degeneration.  This  noxious  agent  primarily  injures 
the  thyroid,  and  secondarily  all  the  organs.  On  the  other  hand,  Bircher, 
Kaufmann,  Scholz,  Kutschera,  and  Dieterle  believe  that  the  thyroid 
disturbances  are  not  solely  the  cause  of  the  disease,  but  that  there  are 
other  determining  causes  of  cretinic  degeneration. 

One  thing  is  certain:  in  every  cretin  the  thyroid  gland  is  not  always 
atrophied,  but  is,  on  the  contrary,  in  some  instances,  hypertrophied. 
Besides  degenerated  portions,  such  enlarged  glands  often  possess  others, 
which  seem  to  be  normal,  and  which,  so  far  as  we  can  judge  by  their 
histological  appearance,  are  undoubtedly  capable  of  function.  After 
going  over  cases  of  cretinism  in  which  microscopic  examination  of  the 
thyroid  has  been  performed,  we  must  conclude  that  there  is  not  always 
a  striking  parallelism  between  the  intensity  of  cretinism  and  the  histo- 
logical disturbances.  As  cretinism  does  not  respond  to  thyroid  opo- 
therapy as  readily  as  other  forms  of  thyroid  insufficiency,  and  on  account 
of  the  above-mentioned  reasons  we  can  conclude  with  Ewald,  Kutschera, 
Bircher,  etc.,  that  endemic  cretinism  is  a  physical  as  well  as  an  intellec- 
tual degeneration  not  solely  due  to  thyroid  insufficiency,  but  to  some 
additional  damaging  influences  on  the  other  organs  of  the  body  as  a 
consequence  of  the  endemic;  in  other  words,  the  pathological  agent  of 
endemic  cretinism  is  polytrope  and  not  monotrope.  This  means  that  in 
order  to  have  a  true  cretinism  we  must  add  to  the  disturbed  thyroid 
function  other  causes.  One  of  the  most  important  of  these  causes  is 
the  fact  that  "the  endemic"  has  been  exerting  its  nocive  influence  upon 


ATHYROIDISM,  INFANTILE  HYPOTHYROIDISM,  CRETINISM     207 

the  organisms  of  these  individuals  throughout  successive  generations. 
The  union  of  all  of  these  conditions  gives,  then,  rise  to  the  true  or  endemic 
cretinism,  whereas  surgical  and  congenital  athyroidism,  spontaneous 
infantile,  and  adult  hypothyroidism  are  caused  only  by  a  thyroid 
insufficiency  and  by  no  other  cause. 

In  cretinism,  as  in  the  other  forms  of  hypothyroidism,  all  degrees  of 
development  can  be  met  with.  If  the  noxious  agent  is  of  benign  type 
the  thyroid  insufficiency  will  be  a  moderate  one,  and  that  condition  may 
remain  stationary  throughout  life.  But  if  the  damaging  agent  is  more 
perfidious  and  affects  individuals  already  in  instable  thyroid  equilibrium, 
cretinism  will  be  more  severe.  All  the  various  stages  found  between 
the  mild  and  the  most  severe  forms  of  cretinism  are  only  links  of  the 
same  chain,  and  Fodere  was  indeed  correct  when  he  said,  "Goiter  is 
only  the  first  degree  of  a  degeneration  whose  last  manifestation  is 
cretinism." 

The  endemic  includes  the  true  endemic  cretinism,  endemic  goiter, 
endemic  deaf  and  dumbness,  and  endemic  feeble-mindedness.  In  opposi- 
tion to  what  is  seen  in  other  forms  of  hypothyroidism,  males  are  more 
often  affected  with  cretinism  than  females. 

Symptoms  of  Congenital  Athyroidism,  Spontaneous  Infantile  Hypothy- 
roidism, and  Cretinism. — As  the  symptomatology  of  congenital  athyroid- 
ism, spontaneous  infantile  hypothyroidism,  and  cretinism,  endemic  and 
sporadic,  on  the  whole  resemble  each  other  very  much,  I  shall  give  the 
clinical  description  of  these  conditions  in  the  same  chapter  in  order  to 
avoid  unnecessary  repetitions.  I  shall  dwell  on  their  respective  charac- 
teristics in  the  chapter  on  Differential  Diagnosis. 

W  hen  any  of  the  above-mentioned  types  of  thyroid  insufficiency  has 
reached  its  full  development  the  clinical  picture  is  so  striking,  so  charac- 
teristic that  a  glance  is  sufficient  to  make  the  correct  diagnosis.  When 
one  has  seen  one  case  he  has  seen  what  is  peculiar  to  all  cases,  no  matter 
what  the  particular  type  may  be.  In  the  first  place,  there  is  on  the  small 
body  of  the  dwarf,  for  such  the  patient  will  be,  an  enormous  head  entirely 
out  of  proportion  to  the  rest  of  the  bod)'.  If  we  add  to  this  a  vague, 
lifeless,  stupid  look  with  a  cretinoid  physiognomy  the  first  impression 
is  complete.  As  for  details  we  may  note  that  the  skull  is  deformed, 
voluminous  in  the  occipital,  and  narrow  in  the  frontal  regions,  and  that 
the  anterior  fontanelle  is  still  persistent  even  in  individuals  fifteen  to 
twenty  years  old.  The  face  is  round,  in  "full-moon,"  and  without 
expression,  the  forehead  low,  receding,  and  furrowed  with  numerous 
wrinkles.  The  nose  is  wide  at  the  basis,  but  short  and  retrousse;  in  a 
word  it  is  what  we  call  expressively  the  "saddle-nose."  The  ears  are 
thick  and  everted.  Both  malar  regions  are  prominent;  the  cheeks,  flabby 
and    hanging,   while   the   lips   are   thick,   cyanotic,   and   everted.      I  he 


208  ATHYROIDISM  AND  IN  FAX  TILE  HYPOTHYROIDISM 

mouth  is  wide  and  open.  The  tongue,  so  thick  that  it  is  too  large  for  the 
oral  cavitv,  protrudes  for  much  of  the  time  from  the  mouth.  Some- 
times it  hangs  out  constantly  and  a  continuous  flow  of  saliva  may  be 
seen  running  out  at  the  corners  of  the  mouth.  This  macroglossia  is  not 
due  to  muscular  hypertrophy  but  is  caused  by  an  abundant  deposit  of  fat 
and  mucine  between  the  muscular  fibers;  it  is  a  sort  of  hpomatous  macro- 
glossia. In  regions  where  goiter  and  cretinism  are  endemic  the  teeth 
are  decayed,  but  in  countries  where  goiter  and  cretinism  are  only  spo- 
radic the  quality  of  the  teeth  of  these  cretins,  according  to  Bayon, 
does  not  differ  very  much  from  that  of  the  teeth  of  normal  children. 
Of  course  in  congenital  hypothyroidism  teeth  are  absent,  second  den- 
tition does  not  in  most  cases  take  place,  and  if  it  does,  it  occurs  only 
very  late,  say  at  the  ages  of  twenty-five  to  thirty  years.  The  neck  is 
short,  and  Hpomatous  masses  are  found  in  the  supraclavicular  spaces. 
The  thorax  is  flat;  the  abdomen  large  and  hanging,  and  has  the  shape  of 
a  "frog-belly."  Umbilical  hernias  are  very  often  present.  The  arms, 
legs,  hands,  and  feet  are  very  stocky,  and  the  swollen  fingers  can  be 
moved  only  with  difficulty.  The  feet  are  short  and  deformed  and  too 
broad  for  their  length;  the  toes  are  swollen,  and  hence  produce  a  peculiar, 
unsteady  and  obviously  difficult  gait.  The  skin  is  pale  and  sallow, 
semitranslucid,  recalling  a  little  the  clinical  picture  of  the  phlegmasia 
alba  dolens.  Even  in  a  very  advanced  period  of  life  the  skin  remains 
unbearded;  the  hair  of  the  pubis  and  axillary  regions  does  not  grow, 
while  the  eyebrows  and  lashes  are  always  spare  and  thin.  The  mucous 
membranes  of  the  larynx,  esophagus,  and  intestinal  tract  are  edematous. 
The  genital  organs,  atrophied  and  arrested  in  their  development,  retain 
the  infantile  type.  If  the  male  cretin  reaches  the  adult  age,  his  testicles 
and  penis  are  considerably  smaller  than  normally.  The  same  is  true 
for  the  uterus  and  its  appendages  in  the  female  cretin.  With  such  a 
hypoplasy  of  the  genital  apparatus,  sexual  appetite  is  not  present. 
The  genital  functions  are  more  or  less  suppressed,  and  only  after  the 
thirtieth  year  do  the  genital  organs  seem  to  develop  sufficiently  to 
functionate,  but  fortunately  these  cretins  are  usually  sterile. 

Nanism  is  one  of  the  earliest  and  most  striking  symptoms  in 
athyroidism  and  spontaneous  infantile  hypothyroidism.  The  expected 
growth  of  the  skeleton  does  not  take  place,  or  if  it  does,  it  occurs  very 
slowly.  Normally  the  length  of  the  skeleton  is  172  cms.  for  man  and 
160  cms.  for  woman.  In  cretins  the  skeleton  varies  from  60  to  120 
cms.  in  length.  For  example,  the  Pacha  de  Bicetre,  nineteen  years  old, 
was  only  90  cms.;  the  cretin  of  Batignolles,  thirty-one  years  old,  was  1 
meter  and  10  cms.  long;  the  cretin  of  Francotte  was  84  cms.  long  when 
twenty-one  years  old;  and  the  one  of  Combe,  80  cms.  when  fifteen  years 
old.     The  bones  are  thick  and  deformed,  as  in  rickets,  and  deformities 


ATHYROIDISM,  INFANTILE  HYPOTHYROIDISM,  CRETINISM    209 

of  the  ribs  and  pelvis  are  frequently  found.  Kyphotic  and  scoliotic 
anomalies  of  the  spine  are  quite  common.  The  skull  of  the  cretin  is 
flat  and  low,  and  wider  than  it  is  high.  The  bones  of  the  skull  are  thick, 
and  prognathism  is  a  characteristic  feature. 

All  cases  of  congenital  athyroidism  are  idiots.  If  athvroidism  or 
hypothyroidism  occurs  at  a  later  period  of  bodily  development,  then 
the  degree  of  idiocy  is  in  direct  proportion  to  the  period  of  development 
in  which  the  thyroid  function  has  become  totally  insufficient. 

In  congenital  athyroidism  and  in  the  most  marked  forms  of  cretin- 
ism the  little  patients  live  a  purely  vegetative  life;  thev  eat,  breathe, 
and  sleep,  and  that  is  all.  They  do  not  even  have  the  instinct  of  conser- 
vation, for  although  suffering  from  hunger  and  thirst  the)'  do  not  have 
the  intelligence  to  take  the  food  that  is  placed  near  them,  and  if  thev 
should  not  be  actually  fed,  they  would  starve  to  death.  Thev  sit  for 
hours,  motionless,  inert,  and  entirely  unconscious  of  the  surrounding 
world,  insensible  to  good  or  bad  treatment,  and  incapable  of  recogniz- 
ing even  their  parents.  They  are  indeed  what  Roesch  calls  the  "man- 
plant." 

If  hypothyroidism  manifests  itself  some  time  after  birth,  namely, 
after  the  child  has  undergone  a  certain  degree  of  physical  and  mental 
development,  the  symptoms  will  be  less  accentuated.  Such  little  patients 
do  recognize  their  surroundings,  and  may  even  smile  when  thev 
see  their  parents,  thus  showing  that  their  cerebral  system  is  able  to 
register  impressions,  although  m  a  very  rudimentary  degree.  It  is  the 
vestiges  of  their  earl\',  but  too  soon  interrupted  cerebral  education,  that 
thev  show  when  they  manifest  signs  of  pleasure  or  discontentment,  or 
when,  for  example,  they  make  efforts  to  grasp  toys  lying  nearby.  Cer- 
tainly they  have  sensations.  Their  psychic  vacuum  is  not  absolutely 
complete  and  they  may  even  have  perceptions.  The)'  have  the  instinct 
of  conservation,  since,  if  food  is  placed  near  them  they  will  take  it. 
The)'  manifest  their  emotions,  and  possibly  their  perceptions,  too,  bv 
grunts  and  growls.  As  a  domestic  animal  may  be  taught,  so  may  they 
be  taught  to  be  clean,  and  they  may  even  be  trained  to  do  things  which 
require  only  a  rudimentary  intelligence,  such  as  to  earn'  wood  or  water. 
The\'  correspond  to  what  Roesch  calls  the  "man-animal."  Of  course 
between  these  extreme  forms  of  hypothyroidism  and  cretinism  and  the 
fruste  forms  all  degrees  are  found.  But,  to  continue,  the  organs  of  sense 
show  a  greatly  diminished  function;  the  senses  <>t  smell,  taste,  and  touch 
are  not  acute;  sensibility  is  considerably  reduced.  The  cretin  will  stand 
for  hours  in  the  full  glare  of  the  sun  and  show  no  signs  of  being  discom- 
forted by  it.  Indeed,  then"  eyes  do  not  seem  to  be  ar  all  affected  by  the 
intense  light.  The)'  hear  and  speak  with  difficulty,  and  quite  often  are 
deaf  and  dumb.  Sometimes  the  speech  consists  only  in  a  few  inarticu- 
14 


210  ATHYROIDISM  AND  INFANTILE  HYPOTHYROIDISM 

late  sounds  which  are  understood  only  by  members  of  the  family; 
when  more  highly  developed  many  seem  to  have  an  especially  great 
difficulty  in  pronouncing  the  consonants.  Their  memory  is  weak.  They 
are  unemotional,  and  in  their  affections  resemble  animals.  If  anyone 
has  been  unkind  to  them  they  do  not  forget  it.  On  the  other  hand,  they 
rejoice  very  much  when,  as  Kocher  says,  "they  see  a  friend  of  their 
stomach."  They  are  very  sensitive  to  cold,  for  not  only  is  the  central 
temperature  reduced,  but  the  peripheric  circulation  is  also  diminished. 
The  blood-pressure  is  low;  pulse  small  and  easily  depressible.  Their 
muscular  system  is  always  poorly  developed;  their  strength  is  in  propor- 
tion to  their  stature  and  their  movements  are  slow  and  awkward.  The 
"frog-shaped"  belly  which  is  often  found  in  cretins  is  no  doubt  caused 
by  this  general  relaxation  of  the  musculature,  and  this  relaxed  condition 
plays  an  important  part,  no  doubt,  in  the  etiology  of  hernias  which  are 
so  frequent  in  cretinism.  Since  they  show  a  profound  dislike  for  any 
physical  effort,  they  sleep  most  of  the  time,  and  for  hours  will  sit  motion- 
less in  the  same  place.  More  than  once  in  the  hospital  ward  I  have 
found  them  sitting  at  the  same  place  where  I  had  left  them  hours  before, 
in  exactly  the  same  posture,  and  totally  indifferent  to  the  external 
world.  Their  appetite  is  moderate,  and  they  have  a  natural  aversion  to 
meat.  Their  digestion  is  bad,  and,  as  a  rule,  they  suffer  from  constipa- 
tion. Cretins  show  great  sensitiveness  to  the  effect  of  alcoholic  drinks. 
In  regions  where  cretinism  is  endemic,  every  little  town,  so  to  speak, 
has  its  "cretin"  (Fig.  82),  and  one  of  the  greatest  amusements  of  the 
unmerciful  and  heartless  youth  is  to  give  a  glass  or  two  of  wine  to  these 
poor  creatures  in  order  to  intoxicate  them  and  then  to  enjoy  their 
contortions  and  queer  faces. 

Differential  Diagnosis. — Since  the  symptoms  of  endemic  and  sporadic 
cretinism,  congenital  athyroidism,  and  spontaneous  infantile  hypothy- 
roidism are  so  much  alike,  differential  diagnosis  is  sometimes  very  diffi- 
cult.    In  the  majority  of  cases,  however,  it  can  be  made. 

Life  in  congenital  athyroidism  is  ordinarily  short.  Death  occurs 
most  usually  during  the  first  two  or  three  years.  According  to  Ewald 
no  case  of  congenital  athyroidism  is  known  to  have  lived  longer  than 
thirty  years,  whereas  some  endemic  cretins  have  acquired  notoriety  by 
reaching  the  ages  of  fifty  or  sixty  years,  and  even  eighty-six  years.  In 
congenital  athyroidism  and  spontaneous  infantile  hypothyroidism  the 
myxedematous  infiltration  of  the  skin  is  very  much  more  marked  than 
in  endemic  cretinism.  On  the  other  hand,  in  the  latter  condition  the 
retarded  growth  and  deformations  of  the  osseous  system  are  less  marked 
than  in  the  former.  A  consideration  of  value  in  differentiating  congen- 
ital athyroidism  from  cretinism  is  the  fact  that  the  latter  condition  occurs 
when  goiter  is  endemic.     To  be  sure,  there  are  sporadic  forms  of  cretin- 


DIFFERENTIAL  DIAGNOSIS  211 

ism  seemingly  occurring  in  regions  where  no  endemic  is  present.  As  a 
rule,  however,  we  nearlv  always  find  in  the  ancestors  of  endemic  and 
sporadic  cretins,  endemic  goiters  or  other  cretinoid  conditions,  serving 
as  telltales. 

In  countries  where  cretinism  is  endemic,  individuals  who  have  goiter, 
who  are  of  small  stature,  and  at  the  same  time  have  a  certain  mental 
deficiencv  are  called  "cretins."  This  appellation  is  not  exact,  as  such 
individuals  are  not  actually  "cretins"  but  cretinoids.  They  represent  a 
higher  step  in  the  scale  of  cretinism  where,  m  fact,  all  degrees  of  cretinic 
degeneration  may  be  found.  Certain  individuals  may,  at  the  first 
glance,  appear  to  be  normal  physically  and  mentally,  yet  their  stature, 
which  is  slightly  under  normal,  their  wide  face,  with  low  forehead,  and 
the  prominence  of  the  malar  bones,  the  slight  touch  of  "saddle-nose" 
and  their  limited  intellectual  power  show  that  these  individuals  have 
been  stamped,  although  lightly,  with  the  endemic.  One  need  only  to 
walk  through  certain  Swiss  valleys  to  become  convinced  of  the  fact  that 
there  are  many  thus  afflicted.  Indeed,  we  may  go  so  far  as  to  say  that  in 
certain  districts  the  entire  population  is  marked  with  the  endemic. 

In  the  first  year  of  life  it  is  extremely  difficult  to  diagnose  cretinism 
or  any  other  form  of  hypothyroidism.  At  that  age  the  child  lives  a 
purely  vegetative  life;  it  is  even  difficult  to  decide  whether  the  child  is 
normal  or  not.  In  fact  the  onlv  symptom  which  might  point  toward 
thvroid  insufficiency  is  a  thick  tongue,  protruding  from  the  mouth,  or 
unusually  thickened  integuments.  Sometimes  the  disease  takes  such  a 
slow  course  that  the  child  reaches  the  second  or  third  year  before  any- 
body realizes  that  something  is  wrong  with  it. 

When  studying  the  embryological  development  of  the  thyroid  we 
saw  that  the  thyroid  gland  at  birth  is  formed  by  a  mass  of  non-difFeren- 
tiated  cells.  No  colloid  is  present,  and  only  in  a  later  period  do  these 
cells  shape  themselves  into  normal  alveoli.  During  this  cellular  anarchy 
it  is  permissible  to  assume  that  the  function  of  the  thyroid  is  greatly 
disturbed,  and  that  it  is  in  a  state  of  hypofunction.  Some  authors,  as 
Langhans,  Kaufmann,  and  Bircher,  go  so  far  as  to  claim  that  tin-  fetal 
thyroid  is  normally  physiologically  inactive.  They  regard  tin*  maternal 
hypertrophy  of  that  gland  as  a  compensatory  process  caused  by  the 
lack  of  thyroid  function  in  the  fetus.  Although  it  is  highly  probable  that 
the  function  of  the  thyroid  during  fetal  life  is  diminished,  it  is,  never- 
theless, difficult  to  admit  that  the  gland  is  in  a  state  of  complete  physio- 
logical negativism.  Let  us  not  forget  that  there  is  a  period,  the  vesicu- 
lar stage,  during  fetal  life  when  well-formed  alveoli  containing  colloid 
are  present.  Nothing  proves  that  the  thyroid  at  that  time  does  not 
functionate.  Furthermore,  it  is  a  well-known  fact  that  pregnant  women 
afflicted   with   hypothyroidism   see  their  symptoms  of   thyroid   msuffi- 


212  ATHYROIDISM  AND  INFANTILE  HYPOTHYROIDISM 

ciency  improve  greatly  during  pregnancy.  This  is  most  likely  due,  not 
only  to  the  hyperplasia  of  their  own  thyroid  but  also  to  a  compensator)' 
function  of  the  thyroid  of  the  fetus. 

The  reason  why  symptoms  of  hypothyroidism  become  noticeable 
only  after  a  certain  period  of  time  after  birth  and  not  at  once,  is  still  a 
debated  one.  Some  think  it  possible  that  during  nursing  the  milk  of 
the  mother  contains  thyroid  products  in  sufficient  quantity  to  supply 
the  ones  lacking  in  the  newborn.  What  seems  to  corroborate  this  view 
is  that  the  symptoms  of  hypothyroidism  become  noticeable  at  the  wean- 
ing time.  Cow's  milk  seems  to  have,  although  in  a  lesser  degree,  the  same 
protective  influence.  On  the  other  hand,  when  meat  diet  takes  the  place 
of  milk  alimentation,  hypothyroidism  symptoms  progress  very  rapidly. 
It  has  been  said  that  the  thymus  supplies  the  thyroid  function  during 
the  first  few  months  of  the  child's  life,  and  then  also  becomes  function- 
ally insufficient.  Possibly,  too,  the  hyperplastic  thyroid  of  the  mother 
has  left  in  the  body  of  the  newborn  enough  active  principles  of  the  thy- 
roid to  be  sufficient  for  a  certain  period  of  time.  Most  likely,  however, 
the  best  reason  is  that  the  symptoms  of  thyroid  insufficiency  are  not, 
and  cannot  be  recognized  in  their  early  development.  Diagnosis  is 
made  only  when  they  have  acquired  a  certain  intensity.  Who  can 
indeed  say  with  a  certainty  that  in  a  few  months  old  child  some  of 
the  manifestations  of  hypothyroidism,  as  for  example  myxedema  and 
stupidity,  are  or  are  not  present  ? 

As  a  rule  typical  hypothyroidism  is  easily  diagnosed.  Some  diffi- 
culty may  be  encountered  in  differentiating  conditions  which  at  first 
resemble  those  seen  in  thyroid  insufficiency.  For  example,  in  certain 
forms  of  extreme  chronic  nephritis,  of  erysipelas  of  the  face,  when  an 
edema  develops  slowly  and  may  cover  large  areas  of  the  body,  a  doubt 
might  arise  in  one's  mind  as  to  their  true  nature,  but  a  closer  examina- 
tion will  solve  the  problem.  At  the  time  of  menopause  a  transient  edema 
may  be  seen,  especially  in  the  face.  It  was  considered  by  Dalche  as  of 
ovarian  origin  and  was  called  by  him  ovarian  pseudomyxedema.  The 
same  author  has  described  a  form  of  cutaneous  infiltration  of  syphilitic 
origin  and  called  by  him  syphilitic  pseudomyxedema.  In  the  familial 
trophedema  Meige  described  a  form  of  cutaneous  infiltration  which 
must  be  regarded  as  of  trophic  origin.  Certain  forms  of  scleroderma 
might,  at  a  superficial  glance,  be  mistaken  for  myxedema,  but  a  more 
accurate  examination  and  palpation  of  the  neck  will  dissipate  all  doubts. 
Adipose  degeneration  of  genital  origin  and  the  one  seen  in  tumors  of  the 
hypophysis  may  sometimes  be  confused  at  first  with  myxedema,  yet  a 
careful  examination  of  the  genital  apparatus  and  the  feminine  aspect 
of  the  individual  will  direct  the  attention  toward  genital  hypoplasia. 
In  tumors  of  the  hypophysis  the  presence  of  headache,    symptoms   of 


DIFFERENTIAL  DIAGNOSIS  213 

compression  on  the  brain,  aided  by  an  x-ray  of  the  skull  will  clear  up 
the  diagnosis. 

Dercum  and  Henry  have  described  areas  of  a  diffuse  general  lipoma- 
tosis more  marked  in  certain  regions  of  the  body,  as  in  the  arms  or  back. 
This  condition  is  accompanied  by  symptoms  of  neuritis  and  is  very 
painful  to  pressure.  It  is  called  adipositas  dolorosa.  Perspiration  may  be 
diminished  or  absent.  Such  cases  may  be  very  difficult  to  differentiate 
from  myxedematous  conditions,  but  the  normal  psyche,  the  absence  of 
edema  in  the  hands  and  feet,  in  short,  the  general  aspect  of  the  patient 
will  prevent  the  mistaking  these  conditions  for  such  as  are  due  to  thy- 
roid insufficiency.  When  doubt  still  exists,  the  thyroid  treatment  will 
throw  some  light  upon  the  subject;  adipositas  dolorosa  does  not  respond 
to  thyroid  opotherapy. 

All  forms  of  dwarfism  are  not  by  any  means  symptomatic  of  hypo- 
thyroidism. Microsomia,  for  instance,  a  condition  in  which  individuals, 
although  of  very  small  stature,  are  perfectly  proportioned,  has  nothing 
to  do  with  thyroid  insufficiency.  As  Bayon  says,  "It  is  a  lusus  natural, 
a  stunt  of  nature."  Bayon  divides  microsomia  into  congenital  and  infan- 
tile. In  the  congenital  form  the  child  is  born  extremely  small,  whereas, 
in  infantile  microsomia,  the  child  is  normal  at  birth,  but  for  some 
unknown  reason  remains  of  extremely  small  stature.  In  both  forms  the 
different  portions  of  the  body,  although  remaining  very  small,  are  still 
proportionate  one  to  another.  Daniels  and  Philipp  compare  one  in  these 
states  to  "a  little  man  seen  through  the  wrong  end  of  an  opera  glass." 

The  great  majority  of  dwarfs  seen  in  vaudeville  theaters  belong  to 
the  infantile  microsomia.  Such  dwarfs  continue  to  grow  gradually  for 
35  to  40  years,  and  often  so  much  so  that  after  a  certain  period  of 
usefulness  on  the  stage  they  are  discarded  because  they  have  grown 
"too  tall." 

Cases  of  chondrodystrophia  fcetalis,  microsomia,  or  achondroplasia, 
have  been  regarded  in  some  instances  as  cases  of  cretinism.  But  if 
chondrodystrophia  foetalis  were  in  relation  to  thyroid  insufficiency,  it 
certainly  should  be  found  much  oftener  in  regions  where  goiter  and 
cretinism  are  endemic.  This  is  not  the  case.  In  fetal  chondrodystro- 
phy, if  the  children  are  not  born  dead,  a  careful  examination  shows  that 
in  such  conditions  symptoms  of  hypothyroidism  are  wanting.  I  he  skin 
is  not  infiltrated;  constipation  is  not  present;  temperature  is  normal; 
tin-  thyroid  gland  can  be  easily  palpated,  and  the  only  deformity  found 
is  that  the  long  bones  are  too  short  in  proportion  to  the  skeleton.  In 
further  development,  the  intelligence  and  genital  apparatus  of  such 
patients  prove  to  be  normal.  The  whole  clinical  picture  is  due  to  ;i 
malformation  of  the  cartilages,  and  not  to  the  thyroid  insufficiency. 
1  he  bones  grow  normally  in  thickness  but  not  in  length. 


214  ATHYROIDISM  AND  INFANTILE  HYPOTHYROIDISM 

In  infantilism  the  osseous  system  and  the  soft  parts  of  the  body 
undergo  their  normal  development;  puberty  only  does  not  appear  and 
the  voung  individual  retains  an  infantile  appearance.  In  recent  years 
Brissaud,  of  Paris,  and  his  pupils  have  described  a  form  of  infantilism 
characterized  by  a  persistence  of  the  juvenile  state  as  to  body,  intellect, 
and  sexuality.  The  face  is  round,  the  body  plump,  and  the  extremities 
small.  This  is  the  Brissaud  type,  but  in  other  cases  the  body  has  a 
slender  shape,  the  extremities  are  thin,  the  face  delicate.  That  is  the 
Lorain  type.  These  conditions  have  nothing  to  do  with  thyroid 
insufficiency. 

There  are  some  idiots  who  present  a  certain  likeness  to  the  Mon- 
golian race.  This  pathological  class  has  been  called  Mongolism.  The 
mongoloid  has  an  inward  and  downward  slanting  of  the  converging  pal- 
pebral fissures.  He  has  some  intelligence  and  is  able  to  utter  more  or 
less  distinctly  a  few  words.  The  tongue  is  not  thickened.  In  opposi- 
tion to  the  real  cretin  who  remains  sometimes  for  hours  motionless, 
Mongoloids  always  show  a  certain  restlessness  in  their  manner.  The 
abdomen  is  distended  on  account  of  obstinate  constipation.  The  large 
fontanelle  closes  between  the  first  and  fifth  year  of  life.  Very  often  they 
have  the  saddle-nose  as  found  in  cretins.  They  are  chicken-breasted. 
There  is  a  great  difference  between  the  skeleton  of  the  mongoloid  idiot 
and  the  genuine  cretin.  In  the  first  case  the  development  of  the  bones 
is  complete,  while  in  the  second  they  are  considerably  retarded.  This 
can  be  easily  demonstrated  by  an  x-ray  picture. 

The  skin  of  the  mongoloid  has  no  myxedematous  appearance.  The 
hair  and  nails  are  normal.  Pfaundler  and  Schlossmann  say,  "The 
intelligence,  which  is  from  the  beginning  only  slightly  developed,  has  a 
tendency  to  continue  on  a  low  level,  but  still  a  distinct  development  is 
present.  The  speech  is  deficient,  notwithstanding  that  the  mongoloids 
understand  their  surroundings  very  well.  They  are  unclean  for  many 
years  and  never  reach  the  degree  of  intelligence  that  appears  in  the 
majority  of  cases  of  myxidiocy  under  thyroid  gland  therapy.  A  short 
comparison  best  shows  the  great  difference  between  mongoloids  and 
myxidiots.  The  mongoloid  has  no  symptoms  of  myxedema  in  later 
years,  no  dwarfish  growth,  no  apathetic,  motionless  manner,  and  none 
of  the  cessation  of  bodily  and  mental  development  peculiar  in  the  myx- 
idiot.  He  is  uncommonly  lively,  dentition  is  normal,  and  he  never 
shows  the  frightful,  repulsive  appearance  of  the  myxocretin.  Thyroid 
therapy  affects  them  absolutely  differently.  The  mongoloid  reacts  only 
in  the  beginning  stage,  not  in  psychic  behavior.  Teething,  fontanelle 
closing,  obesity,  protrusion  of  the  tongue  are  immediately  and  strikingly 
improved  in  the  myxidiot,  only  partly,  often  not  at  all,  in  the  mongoloid." 

According  to   Bayon,  in   microcephalia  the  patients  have  a  normal 


DIFFEREXTIAL  DIAGXOSTS  215 

stature,  but  the  cranial  circumference  is  below  52  cms.,  and  they  pos- 
sess a  brain  whose  weight  is  less  than  1100  gms.  These  measurements, 
however,  have  really  no  great  importance.  More  than  once  the  brains 
of  the  most  hopeless  cretins  have  been  found  to  have  the  same  weight 
as  a  normal  brain,  whereas  people  with  normal  or  even  superior  intelli- 
gence have  been  known  to  have  brains  quite  below  the  normal  weight. 

Microcephalia  should  not  be  confused  with  hypothyroidism,  as  in  the 
first  instance  the  cranium  is  small,  whereas  in  athyroidism  and  cretinism 
the  skull  is  abnormally  large  for  the  small  stature.  As  a  rule  the  micro- 
cephalic patients  are  alert  and  vivacious  which  is  just  the  opposite  to 
what  is  found  in  cretinism.  Furthermore,  no  myxedema  is  found  in 
microcephalia. 

Hydrocephalia  has  been  confused  sometimes  with  hypothyroidism 
and  cretinism,  yet  this  condition  has  no  etiological  relation  whatever 
to  thyroid  insufficiency. 

Rickets  has  been  mistaken,  too,  for  cretinism,  and  Hertoghe  declares 
infantile  hypothyroidism  and  rickets  to  be  identical  pathological  pro- 
cesses. A  closer  examination  of  these  two  conditions  soon  convinces 
one  that  such  a  statement  is  not  true.  In  rickets  the  cartilage  between 
the  shaft  and  the  epiphysis  of  the  long  bones  is  greatly  thickened,  the 
line  of  ossification  very  irregular,  more  spongy  and  more  vascular  than 
normal.  Beneath  the  periosteum,  which  strips  off  easily,  there  is  an 
osteoid  tissue  resembling  decalcified  bone.  In  cretinism  the  cartilages 
are  thin,  and  poorly  supplied  with  bloodvessels;  the  line  of  ossification 
is  very  regular  and  linear.  In  rickets  the  intelligence  of  the  patient  is 
intact  and  the  thyroid  is  normal.  As  Bayon  says,  "  Rachitism  is  a 
disease  of  civilized  centers,  while  cretinism  is  a  disease  of  the  poor, 
ignorant  villages  scattered  in  the  mountains  and  valleys."  Of  course 
both  conditions  might  be  encountered  in  the  same  individual. 


CHAPTER   XVI. 
SMALL  THYROID   INSUFFICIENCY. 

Besides  the  glaring  symptomatology  due  to  absence  or  diminution 
of  thyroid  function  and  which,  as  we  have  seen,  produces  all  forms  of 
hypothyroidism  and  cretinism,  there  is  a  train  of  symptoms,  more  mild 
and  less  conspicuous,  caused  by  a  mild  degree  of  thyroid  insufficiency. 
Just  as,  for  example,  in  renal  disturbances,  besides  the  big,  more  obvious 
symptoms  of  renal  insufficiency,  there  are  small,  less  apparent  ones,  so 
the  same  is  true  in  hypothyroidism.  Besides  the  big  class  of  symptoms 
of  thyroid  insufficiency,  we  find  another  class  scarcely  sketched,  or  very 
atypical.  To  the  first  class  belong  athyroidism,  hypothyroidism,  and 
cretinism;  to  the  second  class  belongs  the  small  thyroid  insufficiency . 

What  is  true  for  all  the  glands  of  the  body  as  the  ovary,  liver,  etc., 
is  true,  too,  for  the  thyroid;  it  may  be  congenitally  weak.  Although  suf- 
ficient to  meet  the  ordinary  physiological  exigencies,  the  thyroid  soon 
becomes  insufficient  when  confronted  with  increased  physiological 
demands  such  as  in  menstruation,  pregnancy,  infections,  etc.;  hence 
symptoms  of  hypothyroidism. 

In  small  thyroid  insufficiency  the  symptoms  are  various  and  multiple. 
They  are  never  all  present  at  the  same  time.  They  may  be  found  in 
earliest  infancy,  such  as  constipation,  flatulence,  and  somnolence,  as 
well  as  in  a  later  period  of  life,  as  baldness,  somnolence,  and  constipa- 
tion. These  symptoms  are  sometimes,  not  always  due  to  thyroid  insuffi- 
ciency. Women  are  more  predisposed  to  them  than  men.  Heredity  is 
also  of  importance,  as  it  is  not  infrequent  to  find  symptoms  only  mildly 
sketched  in  the  mother,  while  they  are  more  intensified  in  the  children;- 
the  reverse  may  be  true,  too.  I  have  seen  a  family  in  which  all  degrees 
of  thyroid  insufficiency  could  be  found,  from  the  mildest  degree  to  a 
well-developed  infantile  hypothyroidism.  The  symptoms  of  thyroid 
insufficiency  were  so  mild  in  one  member  of  the  family  that  almost 
everyone  would  consider  it  as  a  joke  of  very  bad  taste  to  call  that  patient 
thyroidly  insufficient.  Yet  the  small  symptoms  of  thyroid  insufficiency 
which  she  complained  of  were  very  suggestive,  and  were  relieved  by 
thyroid  opotherapy. 

The  part  played  by  consanguinity  in  the  development  of  hypo- 
thyroidism has  been  well  demonstrated  by  Hertoghe. 

Caloric  disturbances  such  as  cold  extremities,  sensation  of  chilli- 
ness, etc.,  are  regarded  by  Hertoghe,  Gauthier,  Levi  and  Rothschild  as 


SMALL   THYROID  IXSUFFICIEXCY  217 

of  thyroid  origin.  Such  patients  are  very  sensitive  to  cold  seasons,  are 
never  warm  enough  in  summer,  do  not  like  draft  and  complain  of  rheu- 
matic pains  and  neuralgia. 

Certain  gastro-intestinal  disturbances  must  be  referred  to  insufficient 
thyroid  function  as,  for  instance,  lack  of  appetite  in  certain  children. 
Such  young  patients  do  not  enjoy  their  meals,  they  care  much  more  for 
sweets  and,  as  a  rule,  do  not  like  bread.  Constipation  is  one  of  their 
chief  complaints.  Constipation  due  to  thyroid  insufficiency  does  not 
differ  materially  from  constipation  due  to  other  causes.  Its  supreme 
test  is  thyroid  treatment.  It  is  found  in  every  stage  of  life  and  in  both 
sexes,  and  is  characterized  by  a  small  stool,  made  of  hard,  drv  fecal 
matter.  It  would  be  an  error  to  claim  that  every  constipation  is  due  to 
thyroid  insufficiency.  When,  however,  every  other  therapeutic  measure 
has  failed,  and  especially  if  at  the  same  time,  some  other  small  symp- 
toms of  thyroid  insufficiency  are  present,  the  thyroid  treatment  must 
be  given  a  trial.  As  was  demonstrated  by  Marbe  in  dogs  with  intestinal 
fistula,  thyroid  opotherapy  increases  the  secretions  of  the  intestinal 
canal,  and  hence  its  evidently  good  influence  on  constipation.  Pos- 
sibly, too,  the  thyroid  has  an  elective  influence  on  the  neuromuscular 
centers  of  the  intestinal  tract. 

As  seen  in  the  chapter  on  Physiology,  the  relations  between  the  thy- 
roid and  the  sexual  apparatus  cannot  be  denied.  We  know  that  normal 
development  of  the  genital  organs  goes  more  or  less  hand  in  hand  with 
a  normal  condition  of  the  thyroid.  This  has  been  abundantly  demon- 
strated clinically  and  experimentally  as  in  athyroidism  and  cretinism 
where  menstruation  remains  absent,  and  pubertv  is  considerably 
retarded. 

On  the  other  hand,  during  menstruation  the  thyroid  becomes  con- 
gested and  enlarged.  This  explains  why  during  menstruation  some 
women  complain  of  a  choking  sensation  and  show  Basedow  symptoms. 

On  the  other  hand,  the  relations  between  the  thyroid  and  pregnancy 
are  well  known  and  the  hypertrophy  of  the  thyroid  seen  in  pregnant 
women  is  not  only  due  to  hyperemia,  but  is  also  caused  by  a  true  hyper- 
plasia. Gauthier,  Parhon  and  Gaulstein  have  shown  that  the  thyroid 
and  ovaries  seem  to  be  antagonistic — the  more  active  the  thyroid,  the  less 
active  is  the  ovarian  function.  Inasmuch  as  during  pregnancy  the  ovarian 
function  is  suspended,  the  thyroid  function  is  increased.  Phis  would 
explain  why  hypothyroidism  is  considerably  ameliorated  during  preg- 
nancy. Of  course,  the  thyroid  of  the  fetus  may  account,  too,  for  this 
amelioration. 

At  the  time  of  menopause  the  ovarian  function  ceases,  the  thyroid 
flares  up  and  becomes  hypertrophied,  causing  nervous  and  psychic  dis- 
turbances to  appear.     However,  after  menopause  has  become  a  well- 


218  SMALL  THYROID  INSUFFICIENCY 

established  fact,  the  thyroid  gland  may  undergo  atrophy;  hence  symp- 
toms of  hypothyroidism. 

In  conclusion  we  can  say  that  the  relations  between  the  thyroid  and 
the  sexual  apparatus  are  very  intimate.  We  must,  consequently,  expect 
to  find  conditions  in  the  genital  apparatus  of  women,  which,  although 
at  first  seemingly  atypical  for  hypothyroidism,  are  nevertheless  etiologi- 
cally  related  to  it.     Let  us  see  if  this  is  true. 

It  is  common  to  see  young  girls  apparently  normal  in  whom  puberty 
is  retarded.  In  some  of  these  cases  of  retarded,  momentarily  suspended 
or  even  totally  suppressed  menstruation,  this  hypo-ovarism  is  due  to 
hypothyroidism.  Infantile  uterus  accompanied  by  hypoplasia  of  the 
ovaries  and  of.  the  entire  genital  apparatus  might  be  regarded,  too,  as 
a  consequence  of  hypothyroidism.  Premature  menopause  followed  by 
subinvolution  of  the  genital  apparatus,  in  other  words,  premature 
senility  of  that  system,  may  also  be  regarded  as  a  consequence  of  hypo- 
thyroidism. In  some  cases  the  disturbances  are  not  objective,  but  only 
functional.  Typical,  for  instance,  is  the  case  reported  by  Levi:  a  lady, 
aged  thirty  years,  who  since  her  puberty  had  menstruated  but  four  or  five 
times  a  year,  and  who  complained  of  baldness  of  the  masculine  type. 
She  was  regarded  by  this  author  as  a  case  of  hypothyroidism  and  treated 
accordingly.  Soon  after  treatment  menstruation  became  regular,  and 
remained  so.  In  the  same  class  is  the  case  reported  by  the  same  author 
of  a  young  girl,  nineteen  years  old,  whose  menstruation  was  constantly 
retarded  or  absent,  and  which  became  regular  after  thyroid  opotherapy. 

Menstruation,  instead  of  being  retarded  or  absent,  may  be  advanced, 
very  abundant,  and  may  last  too  long  a  time.  In  such  cases  menstrua- 
tion is  transformed  into  menorrhagia.  In  other  cases  menstruation  is 
advanced  and  abundant,  but  its  duration  is  not  increased.  Some  other 
times  there  is,  as  in  one  of  my  cases,  a  constant  serobloody  discharge 
lasting  for  years.  Dysmenorrhea,  when  no  other  cause  can  be  found, 
may  be  regarded  as  a  form  of  thyroid  insufficiency.  Sterility,  too,  may 
be  in  certain  cases  benefited  by  thyroid  opotherapy.  Hertoghe  believes 
that  sometimes  abortions,  when  not  due  to  syphilis,  tuberculosis,  or 
some  other  cause,  may  be  regarded  as  some  manifestation  of  hypo- 
thyroidism. These  views  are  corroborated  by  the  fact  that  in  endemic 
goiter  and  cretinism,  abortions  are  extremely  frequent. 

Hertoghe  also  believes  that  retarded  growth  of  the  osseous  system  in 
rickets,  heredosyphilis,  etc.,  is  directly  or  indirectly  due  to  thyroid 
insufficiency.  Infections  and  intoxications  affect  primarily  the  thyroid, 
hence  their  influence  on  the  growth  of  the  skeleton.  Gauthier  was  the 
first  to  call  attention  to  the  fact  that  retarded  consolidation  in  fractures 
might,  in  certain  instances,  depend  upon  thyroid  insufficiency.  Here, 
again,   before   using    the    medication,   every   other   possibility,   such   as 


SMALL   THYROID  INSUFFICIENCY  219 

interposition  of  muscular  fibers  between  the  fragments,  syphilis,  etc., 
which  might  interfere  with  consolidation,  should  be  carefully  investi- 
gated, and  only  when  everything  has  failed,  should  thyroid  medication 
be  resorted  to. 

Certain  forms  of  dermatosis  such  as  acne,  herpes,  eczema,  psoriasis, 
scleroderma,  etc.,  may  in  certain  instances  depend  upon  thyroid  insuffi- 
ciency. This  to  a  certain  extent  seems  plausible,  as  we  know  that  the 
thyroid  has  an  undeniable  influence  over  the  nervous  system  and  the 
metabolism  in  general. 

A  number  of  other  conditions  might  be  regarded  as  the  consequence 
of  thyroid  insufficiency.  It  would  take  me  too  far  to  go  into  more  details. 
Those  who  might  be  interested  in  these  questions  may  look  them  up 
with  great  benefit  in  Hertoghe,  G.  Gauthier,  Levi  and  Rothschild. 

I  should  not  like  to  be  understood  as  saying  that  every  case  of 
retarded  consolidation,  even'  trouble  of  the  genital  apparatus,  every 
disturbance  of  the  gastro-intestinal  tract,  or  every  skin  disease  is  the 
consequence  of  thyroid  insufficiency,  and  that  thyroid  treatment  is  the 
only  one  indicated  in  such  conditions.  I  say  only  that,  according  to  my 
knowledge  along  that  line,  and  according  to  the  wide  experience  of  such 
other  authors  as  Hertoghe,  Gauthier,  Levi  and  Rothschild,  there  are 
certain  conditions  which  may  be  greatly  benefited  by  thyroid  treat- 
ment; this  treatment,  however,  should  be  resorted  to  only  when  a  care- 
ful differential  diagnosis  with  other  possibilities  has  been  made,  and 
only  when  other  therapeutic  measures  have  failed.  In  certain  instances 
the  facies  of  the  patient,  his  mental  development,  an  exaggerated  adi- 
positas,  or  some  other  symptoms  of  thyroid  insufficiency  may  point  out 
the  real  cause  for  the  pathological  conditions  with  which  one  is  con- 
fronted. But  many  other  times  no  sign  of  hypothyroidism  whatsoever 
is  found  which  might  put  the  physician  on  the  right  scent.  In  such 
cases,  if  every  other  therapeutic  measure  has  been  tested,  it  will  do  no 
harm,  and  may  do  a  great  deal  of  good,  to  try  thyroid  treatment. 


CHAPTER  XVII. 
ETIOLOGY  OF   ENDEMIC  GOITER  AND   CRETINISM. 

Historical. — Despite  all  modern  investigations  and  researches  the 
etiology  of  endemic  goiter  still  remains  one  of  the  most  obscure  of  medi- 
cal problems.  The  disease  is  probably  as  old  as  the  human  race  and  is 
mentioned  in  the  literature  of  the  earliest  people.  The  Atharva  Veda, 
an  ancient  Hindu  collection  of  incantations  dating  2000  years  before 
Christ,  contains  extensive  forms  of  exorcism  for  goiter. 

It  is  evident  from  the  writings  of  Vitruvius  and  Juvenal,  that  goiter 
was  known  to  them.  Vitruvius  says,  "Guttur  homini  intumescit  prae- 
sertim  apud  agricolas  Italiae  et  medullos  Alpinos."  (Maurienne  et 
Tarentaise)  and  Juvenal  writes  in  a  passage  of  his  Satires,  "Quis  tumidum 
guttur  miratur  in  Alpibus."  Marco  Polo  relates  in  his  travels  (13th 
century)  that  goiter  is  prevalent  in  the  plateau  of  Central  Asia.  Dur- 
ing the  Renaissance  the  observations  of  the  Swiss  physician  and  alchem- 
ist Paracelsus  (1493-1541)  are  especially  noteworthy  not  only  because 
of  his  excellent  description  of  the  malady  in  the  region  of  Salzburg,  an 
important  focus  to  this  day,  but  also  because  therein  attention  is  first 
called  to  the  existing  relationship  between  goiter  and  cretinism,  and  the 
earliest  positive  information  given  concerning  the  latter  disease.  The 
literature  of  the  16th  and  17th  centuries  offers  little  of  interest  on  this 
subject.  Hirsch  gives  a  list  of  authors  who  report  concerning  the  occur- 
rence of  goiter  and  endemic  goiter  centers  in  the  Alps,  in  the  Pyrenees, 
in  Hungary,  in  the  Atlas  Mountains,  in  Peru,  in  Guatemala,  in  Sumatra, 
in  the  Harz,  and  Riesengebirge,  etc.  None  of  such  writers,  however, 
treated  the  subject  from  a  more  comprehensive  point  of  view  or  studied 
the  question  scientifically.  It  is  true  that  in  1779  Saussure  furnished 
us  with  some  interesting  observations  in  his  Voyage  dans  les  Alpes, 
but  we  are  indebted  to  Malacarne,  of  Turin,  for  the  first  scientific  treat- 
ment of  the  subject  in  the  report  of  his  observations  in  the  Valley  of 
Aosta,  published  in  1789  (Torino,  1789,  Sni  Gozzi  e  Sulla  Stupidita). 
In  1793  appeared  Fodere's  basic  essay  on  Goiter  and  Cretinism  in 
the  Maurienne  and  Aosta  Valley,  and  in  1800  his  Treatise  on  Goiter  and 
Cretinism.  Following  closely  upon  this  we  have  the  work  of  Coindet 
and  Maunoir  at  Geneva  (1815-1822);  of  Rambuteau,  Imperial  Prefect 
in  the  Valais,  and  of  Iphofen  in  Saxony  (1810-1818). 

Toward  the  middle  of  the  last  century  the  importance  of  the  ques- 
tion from  a  sociological  point  of  view  was  officially  recognized  and  in 
1848  the  Sardinian  Government  named  a   commission   for  the  purpose 


DISTRIBUTION  OF  ENDEMIC  GOITER  AND  CRETINISM      221 

of  investigating  the  causes  of  endemic  goiter  and  of  finding  a  remedy 
for  the  disease.  This  example  was  followed  in  1864  by  the  French 
Government.  These  commissions,  after  several  years  of  research,  pro- 
duced elaborate  reports  which  threw  little  new  light  upon  the  question 
but  seemed  to  establish  as  a  scientific  fact  the  popular  belief  in  the 
hydric  origin  of  goiter. 

Since  earlv  in  the  19th  century  there  has  accumulated  such  a  wealth 
of  goiter  literature  that  it  is  impossible  to  enumerate  all  of  these  publi- 
cations. In  the  Index  Catalogue  of  the  Surgeon-General's  Office,  U.  S. 
Army,  not  less  than  1857  publications  are  enumerated  under  Cretinism, 
Goiter,  and  Thyroid  Gland.  Recently  M.  Scholz  mentions  2486  publi- 
cations concerning  cretinism  alone.  A.  Hirsch,  in  his  Study  of  the 
Historical  and  Geographical  Relations  of  Goiter,  has  given  an  admirable 
and  in  many  respects  still  unsurpassed  recital  of  the  historical  develop- 
ment and  various  endemic  and  epidemic  occurrences  of  the  disease.  In 
1908  Switzerland  created  a  goiter  commission  presided  over  by  M. 
Schmidt,  Director  of  the  Federal  Bureau  of  Hygiene,  Berne.  Italy  has 
recently  followed  this  example,  and  both  commissions  are  supposed  to 
work  along  experimental  lines  which  cannot  fail  some  day  to  throw  light 
upon  this  still  obscure  question. 

Geographical  Distribution  of  Endemic  Goiter  and  Cretinism. — Perhaps 
to  no  other  disease  can  the  term  endemic  be  so  appropriately  applied 
as  to  goiter.  Entire  districts  are  so  intensely  affected  that  a  large  pro- 
portion of  the  inhabitants  are  goiter-bearers,  the  disease  affecting  ani- 
mals as  well  as  human  beings.  The  limitations  of  the  areas  subjected  to 
the  endemic  are  so  sharply  defined  that  sometimes  a  hill,  river,  or  even 
a  street,  may  form  the  dividing  line  between  the  goiterous  locality  and 
immune  territory. 

Further  demonstration  of  the  localized  character  of  the  malady  can 
be  found  in  the  numerous  examples  of  individuals  from  goiter-free  dis- 
tricts who  rapidly  acquire  thyroid  enlargements  while  living  in  regions 
of  goiter  endemicity,  and  who  recover  on  removing  to  immune  terri- 
tory, or  vice  versa,  in  the  numerous  cases  of  goiter-bearers  who  remove 
from  the  endemic  region  sufficiently  early  in  the  development  of  the 
disease  before  colloid  and  cystic  changes  have  ensued  in  the  gland,  when 
the  tendency  is  for  the  struma  to  disappear.  Thus,  according  to  Guyon, 
emigrants  from  the  Canton  of  \  alais,  lost  their  goiters  in  Algiers;  and 
Hubner  reports  that  16,000  emigrants  from  the  district  of  Sal/burg,  in 
general  goiterous,  saw  this  infirmity  disappear  after  settling  in  Prussia. 
Cardinal  Billiet  writes,  "When  an  infected  family  moves  to  a  parish 
not  in  endemic  territory,  such  goiters  as  are  not  too  severe,  disappear 
gradually,  and  in  the  second  or  third  generation,  this  family  will  acquire 
normal  thyroid  glands." 


222  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

Endemic  foci  are  distributed  over  all  the  inhabited  portion  of  the 
earth's  surface.  So  closely  associated  with  goiter  is  the  distribution  of 
cretinism  that  the  geographical  occurrences  of  both  forms  of  disease  can- 
not be  easily  separated,  and  are  most  comprehensively  and  adequately 
treated  together.  In  Europe  the  center  of  highest  endemicity  for  goiter 
and  cretinism  is  to  be  found  in  the  Middle  Alps,  whence  it  radiates  in 
diverse  directions.  There  are  numerous  other  foci  in  connection  with 
different  ranges  or  deep-lying  river  valleys  as  the  Carpathian,  Pyrenees, 
etc.  But  even  within  these  areas,  the  endemic  is  not  uniformly 
distributed. 

In  Switzerland,  the  Canton  of  Valais,  the  valleys  of  the  Rhone  and 
its  tributaries  are  centers  of  high  endemicity.  The  Valley  of  the  Reuss 
in  the  Canton  of  Uri,  and  the  Valley  of  the  Aare  in  the  Canton  of  Aarau 
are  severely  affected.  The  endemic  is  most  intense  in  the  Cantons  of 
Berne,  Argovy,  and  Fribourg;  no  canton,  however,  is  completelv  immune. 
According  to  Bircher,  from  22  to  50  per  cent,  of  the  school  children  and 
from  15  to  30  per  cent,  of  the  recruits  are  goiterous  in  the  districts  on 
the  right  bank  of  the  river  Aare.  The  statistics  furnished  by  Kocher 
show  from  80  to  90  per  cent,  of  the  school  children  of  Berne  to  be 
goiterous. 

The  endemic  is  intense  in  the  valleys  radiating  from  Mont  Blanc 
into  Lombardy,  and  from  the  Alps  of  Savoy  into  the  neighboring  depart- 
ments of  the  Basses-Alps,  the  Maritime  Alps,  the  Haute-Garonne,  etc., 
where  both  goiter  and  cretinism  are  prevalent. 

The  extent  of  the  social  and  economic  loss  due  to  the  goiter  endemic 
in  European  countries  is  scarcely  appreciated.  As  we  know,  goiter  and 
cretinism  go  hand  in  hand.  As  early  an  observer  as  Fodere  remarked 
that  "goiter  is  the  first  degree  in  a  degenerative  process  of  which 
cretinism  is  the  last  step,"  and  since  then  the  majority  of  scientific 
investigators  have  adopted  the  same  conclusions. 

Fodere,  MafFei,  Roesch,  Traxler,  Morel,  Lombroso,  Milani,  Marchant, 
Lourdes,  Koestl,  and  Chabrand  consider  the  causal  factors  of  both 
diseases  identical.  MafFei  calls  goiter  the  "precursor  of  cretinism," 
Roesch  considers  it  the  "first  link  in  the  chain  of  degrees  and  forms  of 
cretinism,"  Morel  says  that  "goiter  is  the  first  stage  on  the  road  that 
leads  to  cretinism,"  and  Niepce  refers  to  goiter  as  the  "first  degree  in  the 
degenerative  process  of  which  cretinism  is  the  final  term."  Other  inves- 
tigators lay  more  stress  upon  the  etiological  relationship,  believing  that 
where  the  endemic  factors  are  light,  goiter  alone  is  to  be  found,  and  that 
where  they  are  severe,  cretinism  appears.  Rambuteau  says,  "The 
causes  of  goiter  and  cretinism  are  the  same,  and  only  differ  in  the  degree 
of  activity,"  and  Milani  affirms  that  "where  only  goiter  is  to  be  found, 
we  can  be  certain  that  the  endemic  factors  are  mild."     We  may  there- 


DISTRIBUTION  OF  EXDEMIC  GOITER  AXD  CRETLXISM      223 

fore  conclude  that  where  goiter  is  at  home,  cretinism  is  rarely  missing, 
and  in  regions  of  high  goiter  endemicity  it  is  frequent.  This  is  true 
not  only  of  the  Central  European  Alpine  region,  but  also  of  the  high 
plateau  of  Middle  Asia  and  all  other  goiter  regions  of  the  earth.  This 
local  and  geographical  joint  occurrence  indicates,  of  course,  an  intimate 
connection  between  the  conditions  of  both  maladies.  Griesinger  writes, 
"Where  the  endemic  is  very  severe,  the  entire  population  is  affected. 
Besides  the  true  cretins,  the  half-cretins,  and  goiter-bearers,  there  are 
innumerable  weak-minded,  miserable,  and  badly  proportioned  indi- 
viduals; there  are  many  deaf-mutes,  stutterers,  and  stammerers,  and 
strabismus  and  deafness  are  frequent.  Through  the  entire  native-born 
population  runs  a  streak  of  physical  degeneration  and  mental  dulness; 
even  those  individuals  who  pass  for  health}'  and  intelligent,  are,  on  the 
whole,  unlovely,  narrow-minded,  and  sluggish,  and  the  country  teems 
with  mean-spirited  phihstines  in  whom  the  qualities  of  heart  are 
insufficient  to  compensate  for  the  lack  of  intellect." 

Often  the  influence  of  the  cretinoid  degeneration  is  to  be  observed 
only  in  symptoms  to  which  ordinarily  no  significance  is  attached,  they 
are  considered  as  racial  peculiarities  or  family  characteristics,  etc.,  but 
not  as  the  sign  of  a  pathological  process  which  they  really  are.  Among 
these  symptoms  must  be  classed,  abnormally  small  stature  with  dispro- 
portionately long  body  and  short  legs,  ugly  repulsive  features,  mean- 
spiritedness,  diminished  mental  faculties,  retarded  development,  etc. 

Close  observers  have  long  ago  noted  that  these  peculiarities  are  not 
accidental,  but  stand  in  close  relationship  with  the  prevailing  endemic 
goiter  and  cretinism. 

That  deaf-mutism  must  be  included  in  the  cretinoid  degeneration 
has  been  scientifically  established  by  the  investigations  of  Bircher  and 
others.  Deaf-mutism  is  to  be  found  elsewhere  than  on  endemic  terri- 
tory, but  is  of  rare  occurrence  and  is  not  associated  with  idiocy.  In 
countries  exempt  from  goiter  there  occur  3  cases  of  deaf-mutism  per 
10,000  inhabitants,  while  in  endemic  centers  it  is  far  more  frequent. 
Among  civilized  countries,  Switzerland  possesses  the  highest  number  of 
deaf-mutes.  The  statistics  of  1 87 1  show  a  general  average  for  the  whole 
country  of  24  per  10,000  inhabitants.  Were  we,  however,  to  separate 
the  endemic  territory  from  the  rest  of  the  country,  the  relative  figures 
would  be  far  higher,  amounting  in  some  regions  to  250  and  more  per 
10,000  inhabitants. 

In  Austria  the  regions  where  severe  goiter  endemics  prevail  suffer 
proportionated  from  an  endemic  deaf-mutism;  in  Salzburg  there  are 
27.8  deaf-mutes  per  10,000;  in  Stvria  20,  and  in  Carmthia  44  per  10,000. 
The  endemic  is  most  intense  in  the  Cannthian  district  ot  St.  \  eit  and 
Wolfsberg  and  in  the  Salzburg  district  ofZell  where  there  are  more  than 


224  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

50  deaf-mutes  per  10,000  inhabitants.  This  coincident  and  parallel 
movement  points  to  a  close  inner  relationship.  These  statistics  as  to 
endemic  deaf-mutism  have  been  drawn  from  H.  Bircher's  monograph 
on  Endemic  Goiter  and  its  Relationship  to  Deaf-mutism  and  Cretinism. 
His  conclusions  are:  "We  must  consider  endemic  deaf-mutism  not  only 
as  an  accompanying  symptom  of  cretinism,  but  also  as  an  intermediate 
form  of  the  cretinoid  degeneration  between  goiter  and  cretinism."  He 
further  says,  "It  is  my  belief  that  endemic  goiter,  deaf-mutism,  and 
idiocy  are  only  different  degrees  and  ultimate  results  of  one  and  the 
same  degenerative  process."  Moreover,  the  endemics  of  these  diseases 
are  invariably  concurrent,  that  is,  the  severer  forms  of  the  degeneration 
such  as  deaf-mutism  and  idiocy  do  not  occur  without  the  milder  form — 
goiter.  But  where  the  endemic  is  slight,  goiter  may  occur  without  deaf- 
mutism  and  cretinism.  In  conclusions  based  upon  investigations  made 
in  the  deaf  and  dumb  asylums  of  Switzerland,  Bircher  states  that  while 
two-thirds  of  the  pupils  in  these  asylums  are  cases  of  endemic  deaf- 
mutism  and  one-third  sporadic,  it  is  safe  to  affirm  that  80  per  cent,  of 
all  deaf-mutism  in  Switzerland  must  be  attributed  to  the  prevailing 
goiter  endemic.  Of  the  pupils  in  Swiss  asylums  for  the  deaf  and  dumb 
72  per  cent,  are  goiterous. 

In  the  Provinces  of  Piedmont,  Lombardy,  and  Venice,  in  1883, 
among  a  population  of  9,565,038  there  were  128,730  goiter-bearers  and 
12,882  cretins.  That  is,  about  1  in  every  67  of  the  inhabitants  was 
either  goiterous  or  cretinous. 

In  the  Tyrol  the  statistics,  made  by  the  Austrian  Government  in 
1883,  show  930  cretins  in  a  population  of  797,040;  the  number  of  goi- 
ters is  not  given.  In  Cisleithania,  Austria,  with  a  total  population  of 
21,840,112,  there  were  in  1883,  12,815  cretins,  or  58.6  per  100,000. 
In  the  District  of  Murau  in  Styria,  where  the  endemic  is  most  intense, 
the  proportion  of  cretins  is  1045  to  every  100,000  inhabitants.  In 
France  Baillarger  estimated  in  1873  that  the  total  number  of  adult 
goiterous  individuals  over  twenty  years  of  age  reached  370,043,  and  that 
of  cretins  about  120,000;  that  is,  in  a  total  population  of  36,000,000  the 
proportion  of  goiter  subjects  was  1.04  per  cent,  and  that  of  the  cretins, 
0.33  per  cent.  These  figures,  however,  change  most  significantly  if  we 
consider  the  regions  where  the  endemic  prevails  with  the  greatest 
intensity  separately;  we  then  find  in  the  department  of  Savoy,  for 
instance,  133.7  goiterous  individuals  per  1000,  and  in  the  valleys  of 
the  Maurienne  and  Tarantaise  respectively,  22.7  and  14.5  cretins  per 
1000. 

According  to  the  statements  of  Mayet  in  1900  these  conditions  as 
given  by  Baillarger  have  not  altered  appreciably.  McCarrison  reports 
that  in  the  part  of  the  Himalayas  where  his  researches  were  carried  out, 


DISTRIBUTION  OF  ENDEMIC  GOITER  AND  CRETINISM       225 

goiter  is  so  common  that  in  some  of  the  villages  it  is  difficult  to  find 
man,  woman  or  child  not  suffering  from  the  deformity.  He  estimates 
that  not  less  than  20  per  cent,  of  the  population  of  Gilgit  suffer  from 
goiter,  and  he  found  in  a  population  of  70,000  over  200  cretins.  In 
Himalavan  India  and  Europe  alone  McCarnson  estimates  the  number 
of  sufferers  from  goiter  at  about  5,000,000.  In  fact  it  cannot  be  suffi- 
ciently emphasized  that  goiter  exercises  an  eminently  destructive  racial 
influence,  and  that  where  it  is  endemic  the  capacity  for  physical  and 
intellectual  work  must  be  seriously  undermined.  Nor  must  it  be  for- 
gotten that  the  mortality  for  endemic  centers  is  considerably  higher 
than  elsewhere. 

In  Tyrol,  Carinthia,  and  Styria  there  are  numerous  goiter  and 
cretin  centers,  the  disease  descending  from  the  mountain  slopes  into 
the  plains  and  appearing  here  and  there  along  the  river  valleys  such  as 
the  Danube,  Enns,  etc.  Despite  the  very  striking  association  of  goiter 
with  mountainous  regions,  it  is  not  confined  to  them.  St.  Lager  tells 
us  that  it  is  prevalent  on  the  plains  of  Lombardy,  of  Piedmont,  and  of 
Alsace;  that  it  occurs  on  the  plains  of  the  Danube  in  Upper  and  Lower 
Austria,  and  that  it  is  met  with  on  the  plains  of  the  Lena  and  Obi  in 
Russia  and  along  the  St.  Lawrence  River  in  Canada;  and  that  it  is  even 
to  be  found  in  some  of  the  oases  of  the  Sahara.  Goiter  is  very  rare  in 
the  North  German  Lowlands,  in  Denmark,  the  Netherlands  and  in  the 
Scottish  Highlands.  In  Sweden,  according  to  Ewald,  there  existed  in 
the  whole  country  in  1867  only  628  goiter-bearers,  of  which  579  were 
to  be  found  in  the  District  of  Falun.  In  France  the  Alpine  Depart- 
ments, the  Vosges,  Cevennes,  the  Pyrenees,  and  the  high  central  plateau 
are  affected. 

The  disease  is  so  common  in  certain  parts  of  England  that  it  has 
been  known  as  the  "Derbyshire  neck."  It  is  especially  prevalent  in 
Derbyshire,  Hampshire,  and  Sussex.  In  Spain  endemic  centers  exist 
in  the  Pyrenees,  Asturia,  and  Galicia.  The  mountains  of  Asia,  Japan, 
and  manv  of  the  Asiatic  Islands  have  numerous  foci.  The  Himalayas, 
the  Cordilleras,  Caucasus,  Ural,  Atlas,  and  Altai  Mountains  all  have  goiter 
centers.  Goiter  occurs  also  upon  islands  like  Ceylon,  Madagascar,  the 
Azores,  Java,  and  Sumatra. 

Goiter  is  to  be  found  in  North  America  where  Munson  has  observed 
closely  circumscribed  endemics  among  the  Indians.  According  to 
Bircher  who  gives  St.  Lager  as  his  authority),  endemics  accompanied 
by  deaf-mutism  prevail  in  the  States  of  Newr  York,  Ohio,  Virginia,  Mich- 
igan, Kentucky,  Tennessee,  Maine,  Vermont,  Connecticut,  Massachu- 
setts, and  New  Hampshire.  There  are  15,000  feeble-minded  in  Ohio. 
In  Wisconsin  endemic  goiter  is  common.  The  region  of  the  Greal 
Lakes  is  reported  by  Dock,  Osier,  and  Ad  a  mi  to  have  numerous 
15 


22(1  ETIOLOGY  OF  ENDEMIC  GOITER  AXD  CRETINISM 

goiter  centers.  Ashmead  tells  of  an  endemic  center  in  Pennsylvania, 
and  Holder,  of  centers  in  Montana,  Dakota,  Mississippi,  and  also 
in  the  vicinity  of  the  Rocky  Mountains.  Marine  finds  the  disease 
widely  disseminated  along  the  Great  Lakes,  not  only  among  human 
beings,  but  also  among  animals.  He  states  that  the  endemic  is  espe- 
cially severe  among  sheep.  According  to  his  investigations,  90  per  cent, 
of  the  street  dogs  of  Cleveland  are  goiterous.  In  the  United  States 
and  Canada  goiters,  though  numerous,  are,  as  a  rule,  not  large,  and 
cretinism  is  rare.  Along  the  shores  of  Lake  Erie,  Adami  speaks  of 
French-Canadian  villages  in  which  scarcely  a  family  is  to  be  found 
without  one  or  more  goiterous  members. 

In  South  America  the  first  explorers  of  New  Granada  were  aston- 
ished to  find  the  banks  of  the  Rio  Magdalena  inhabited  by  a  race  of 
heavy  and  stupid  savages  of  sluggish  habit  who  passed  their  days  in 
sleep.  Among  the  goiterous  Indians  of  the  Peruvian  plateau,  cretinism 
had  reached  such  a  degree  that  it  required  nothing  less  than  a  papal 
bull  from  Paul  III  to  convince  the  missionaries  that  these  were  indeed 
men  with  souls  to  be  evangelized. 

In  Brazil  the  river  which  divides  the  provinces  of  Corrientes  and 
Entre-Rios  is  called  the  Guay-qui-raro  or  "thick-neck  maker"  by  the 
Indians,  a  convincing  testimony  as  to  the  existence  of  the  endemic  in 
these  regions. 

In  the  Balkans  the  Struma  River,  along  which  heavy  fighting  has 
been  taking  place  during  this  great  world  war,  is  called  "Struma" 
because  of  the  prevalence  of  goiter  along  its  banks  and  tributaries. 

It  has  been  asserted  by  Saussure  and  Demme  that  goiter  was  not 
to  be  found  above  an  altitude  of  from  3000  to  3600  feet,  and  Demme  and 
Maffei  maintain  that  it  does  not  occur  under  900  feet.  We  know  both 
of  these  theories  to  be  untenable.  McCarnson  met  with  goiter  at 
10,000  feet  in  the  Himalayas,  and  we  have  reliable  information  as  to 
its  existence  up  to  an  altitude  of  15,000  feet  (Nepal,  Kemaon,  Kash- 
mir, etc.),  and  at  6000  feet  in  Savoy  as  well  as  on  the  high  plateaus  of 
Bolivia  and  Peru. 

The  mountainous  regions  of  the  Upper  Tonking,  Laos,  and  Yunnan, 
as  shown  by  Clavel,  Simon,  Billet,  and  Jouveau-Dubreuil,  may  be  con- 
sidered as  one  of  the  great  boulevards  of  goiter  just  as  severely  affected 
as  the  Alps  and  Himalayas.  In  1896  Billet  wrote  of  Kao-Bang,  "This 
affection  is  extremely  common  among  the  native  population  inhabiting 
the  rocky  amphitheaters  and  deep  gorges  of  Upper  Kao-Bang." 


MILITARY  SIGNIFICANCE  OF  ENDEMIC  GOITER  227 

ECONOMICAL,  SOCIAL  AND  MILITARY  SIGNIFICANCE  OF  ENDEMIC 
GOITER    AND    CRETINISM. 

In  an  interesting  article  on  goiter  as  an  economic  loss,  Dr.  Oswald 
writes,  "If  we  allow  the  military  statistics  of  Switzerland  to  speak  for 
themselves,  we  shall  see  that  an  average  of  17CO  recruits,  i.  <?.,  7  per 
cent,  are  annually  pronounced  unfit  for  military  service  because  of  goi- 
ter, and  400  drilled  soldiers,  i.  e.,  2  per  1000,  are  annually  discharged 
from  the  service  because  of  the  same  maladv.  Because  of  idiocv,  180 
conscripts  are  annually  rejected.  The  medical  conception  of  idiocv 
includes  man)'  conditions,  but  it  is  certainly  not  too  much  to  attribute 
half  of  this  number  to  cretinism,  which  gives  us  the  figure  of  90.  Eighty 
recruits  are  annually  rejected  on  account  of  deaf-mutism,  two-thirds  of 
which  number  must  be  considered  as  due  to  cretinoid  conditions,  and 
this  gives  us  the  number  of  52  to  be  included  in  our  calculations. 
Because  of  insufficient  stature,  1900  recruits  are  annually  rejected  from 
military  service,  of  which  number  at  least  one-half  must  be  attributed 
to  the  cretinoid  degeneration,  so  we  again  have  the  number  of  950. 
By  adding  these  figures  together,  we  obtain  the  very  considerable  total 
of  3000  recruits  annually  rejected  because  of  the  goiter  endemic  and 
should  we  continue  our  calculations  through  the  ten  years  of  Swiss  mili- 
tary duty,  we  come  to  the  enormous  figure  of  30,000  or  nearly  one- 
fourth  of  the  Swiss  Army."  Bircher  calculates  the  loss  to  the  Swiss 
army  due  to  the  goiter  endemic  at  one-sixth  of  its  total  force.  In  France, 
out  of  a  total  of  300,000  recruits,  1200  are  annually  rejected  because  of 
goiter.  In  Italy  3  per  cent,  of  the  conscripts  were  rejected  from  mili- 
tary service  between  the  years  1 859-1 864  because  of  goiter  and  cretinism. 

It  is  self-evident  that  these  figures  have  an  economical  as  well  as  a 
military  significance.  It  is  hardly  necessary  to  mention  that  cretins, 
the  feeble-minded,  the  deaf  and  dumb,  become  in  one  way  or  another  a 
burden  upon  society.  Although  the  demands  which  military  service 
make  upon  the  capacity  for  work  are,  of  course,  greater  than  in  tin- 
ordinary  occupations  of  civil  life,  there  are  many  large  industries  which, 
on  general  principles,  do  not  employ  young  men  who  have  been  rejected 
from  military  service,  and  while  young  men  of  this  class  may  be  for  a 
time  unhindered  in  their  callings,  they  are  often  ultimately  obliged  to 
seek  an  easier  occupation  because  of  infirmities  due  either  directly  or 
indirectly  to  their  goiters. 

In  these  figures  women  have  not  been  taken  into  consideration,  and 
they  are,  as  we  know,  more  severely  affected  than  men  by  the  endemic. 
Baillarger  has  estimated  that  in  France  the  relative  proportions  as  to 
sex  incidence  are  approximately  2  :  5,  but  where  the  endemic  is  intense, 
the  number  of  goiterous  men  more  nearly  approaches  that  of  the  women. 


228  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

The  main  bulk  of  the  population  is  not  included  in  these  calculations, 
but  although  it  is  impossible  to  secure  such  comprehensive  and  reliable 
statistics  for  the  entire  population,  these  military  statistics  are  sufficiently 
illuminating  as  to  the  enormous  drain  upon  the  defensive  and  economical 
resources  of  certain  countries. 

GOITER    EPIDEMICS. 

Goiter  epidemics  usually  occur  in  endemic  territory,  or  at  least,  in 
regions  where  sporadic  goiter  is  not  rare,  and  are  most  frequently  to  be 
observed  in  groups  of  young  people,  newcomers  to  the  goiterous  locality. 
These  epidemics  have  been  exclusively  observed  in  barracks,  boarding 
schools,  seminaries,  prisons,  or  other  agglomerations  of  individuals  in 
crowded  space,  and  do  not  affect,  as  a  rule,  the  general  population. 

The  first  in  date  of  these  epidemics  was  noticed  by  Forster,  ship's 
surgeon  with  Capt.  Cook  in  1772.  While  the  ship  was  floating  among 
icebergs,  the  crew  collected  pieces  of  the  ice  and  melted  them  for  drink- 
ing purposes.  The  exterior  only  was  salty,  and  when  this  had  been 
melted  away,  the  water  obtained  was  sweet  and  palatable,  and  evidently 
of  fresh-water  origin.  All  of  the  crew  who  drank  of  this  water  suffered 
from  swelling  of  the  thyroid  gland,  but  those  who  refrained  from  using 
it  were  not  affected.  Since  this  epidemic  occurred  in  midocean,  St. 
Lager  thinks  it  cannot  be  associated  with  endemic  goiter,  whereas, 
Bircher  argues  that  the  ice,  having  been  of  fresh-water  derivation,  was 
probably  formed  in  some  goitenferous  river.  As  it  is  a  well-known  fact 
that  microorganisms  resist  the  low  temperature  of  ice,  he  considers  that 
the  Cook  epidemic  belongs  in  the  endemic  class.  Repin,  on  the  con- 
trary, thinks  that  this  case  has  no  connection  with  endemic  goiter  and 
is  to  be  considered  as  a  congestion,  "a  frigore,"  such  as  appears  suddenly 
among  soldiers  after  drinking  glacier  water.  According  to  my  judgment, 
Bircher's  view  is  the  preferable  one. 

Meyer-Ahrens  reports  an  epidemic  occurring  in  a  military  school  in 
Kronstadt  (Siebenbiirgen)  in  1784.  Of  the  38  pupils,  36  became  goiter- 
ous in  a  short  time,  and  2  of  the  7  adults  in  the  institution  acquired 
goiters.  The  drinking  water  could  not  be  incriminated  as  it  was  the 
purest  in  Kronstadt,  and  was  used  outside  of  the  institution  without 
deleterious  results.  Investigations  were  therefore  made  as  to  the  hygi- 
enic conditions  within  the  buildings,  and  as  a  result,  the  rooms  were 
found  to  be  small,  badly  ventilated,  and  overcrowded.  With  a  change 
of  quarters  and  an  amelioration  of  these  conditions,  the  epidemic  disap- 
peared. Another  epidemic  is  reported  by  Valentin  and  cited  by  Ewald 
and  H.  and  E.  Bircher.  Early  in  the  year  1783  an  infantry  regiment 
was  transferred  to  Nancy  where  the  endemicitv  is  slight.     During  the 


GOITER  EPIDEMICS  229 

winter  of  the  same  year,  which  was  remarkable  for  its  sudden  changes 
of  temperature  and  general  bad  weather,  38  men  of  this  regiment  acquired 
goiter;  in  1785,  205  men  became  goiterous;  in  1786  there  were  425  cases; 
in  1787  the  number  of  cases  had  diminished  to  257;  in  1788  to  132; 
and  in  1789  the  epidemic  terminated  with  43  cases.  It  is  especially 
noteworthy  that  in  this  epidemic  only  the  common  soldiers  were 
attacked,  the  officers,  corporals  and  sergeants  remaining  exempt  from 
the  disease,  although  living  in  the  same  barracks  and  making  use  of  the 
same  drinking  water.  This  exemption  has  been  attributed  to  the  fact 
that  the  officers  and  non-commissioned  men  drank  wine,  while  the 
common  soldiers  were  obliged  to  satisfy  their  thirst  with  water.  As  my 
observations  have  not  convinced  me  that  the  common  soldier  is  more 
addicted  to  drinking  water  than  his  superior  officer,  this  theory  does 
not  seem  to  me  conclusive.  Taussig  thinks  the  explanation  of  this 
immunity  is  to  be  sought  rather  in  the  more  isolated  lodgings  of  the 
officers  and  their  less  frequent  and  close  contact  with  the  soldiers  suffer- 
ing from  the  epidemic.  He  regards  this  case  as  evidence  in  favor  of  the 
infection  by  contact  theory,  of  which  he  and  Kutschera  are  adherents. 
The  epidemic  which  occurred  in  the  fortress  of  Silberberg  in  Silesia 
during  1819  has  been  given  a  detailed  and  still  interesting  description 
by  the  regimental  surgeon,  Haneke.  Goiter  is  still  endemic  in  the  town 
of  Silberberg  (Eulengebirge),  and  even  at  that  time  the  drinking  water 
was  regarded  as  the  principal  etiological  factor.  Haneke  states  that  the 
recruits  were  drawn  from  immune  territory,  and  that  after  scarcely 
three  weeks'  residence  in  the  fortress,  many  of  the  voung  soldiers  com- 
plained of  oppression  and  shortness  of  breath  in  mountain  climbing. 
Examination  of  these  men  showed  the  thyroid  gland  to  be  swollen,  but 
still  soft.  As  they  were  otherwise  in  good  health,  Haneke  recommended 
that  they  be  permitted  to  perform  their  service  with  open  collars.  The 
number  of  those  affected  augmented  so  rapidly  that  earlv  in  1820  some 
20  odd  were  admitted  to  the  hospital,  the  thyroid  gland  having  acquired 
such  volume  that,  even  with  open  collars,  it  had  become  impossible  on 
account  of  dyspnea  for  the  soldiers  to  perform  their  military  service. 
During  the  following  summer  the  development  of  the  disease  was  slow, 
but  in  the  ensuing  autumn  which  was  exceedingly  damp,  cold  and  stormy, 
the  epidemic  rapidly  assumed  such  proportions  that  out  of  the  }*o 
composing  the  battalion,  60  had  been  reported  goiterous  by  November 
17,  and  on  November  20,  three  days  later,  this  number  had  increased 
to  100  and  augmented  steadily  until  December,  when  only  70  of  the 
battalion  were  exempt.  Haneke  further  states  that  those  individuals 
who  used  only  boiled  water,  very  rarely  showed  any  swelling  of  the 
thyroid  gland,  and  that  where  a  slight  enlargement  occurred,  it  never 
developed  into  a  real  goiter.     Eventually  the  epidemic  became  so  severe 


230  ETIOLOGY  OF  EXDEMIC  GOITER  AXD  CRETINISM 

that  the  battalion  was  transferred  to  Schweidnitz  where,  within  a  short 
time  after  removal  from  the  goitengenous  influences,  the  condition  of 
the  men  improved  and  all  traces  of  the  goiters  acquired  in  Silberberg 
disappeared,  except  in  those  cases  where  chronic  changes  had  ensued. 

In  citing  this  epidemic,  Schittenhelm  and  Weichardt  remark  that, 
"Young  adolescent  recruits  from  the  Polish  plains  were  subjected  to 
those  intensely  goiterigenous  influences,"  and  they  furthermore  add, 
"It  is  peculiarly  significant  for  our  conception  of  the  etiology  of  goiter 
that  these  young  people,  belonging  to  a  population  totally  exempt  from 
the  endemic,  should  be  so  acutely  and  subacutely  affected  by  the 
disease." 

Epidemics  were  observed  in  1859-61-63  in  Colmar  when  different 
regiments  were  successively  attacked,  first  the  cuirassiers,  then  the  infan- 
try and  cavalry.  Epidemics  occurred  repeatedly  in  the  barracks  of 
Briancon  during  1812,  1819,  1826,  1841,  1842,  1850,  1857,  i860,  and 
1863.     These  have  been  reported  by  Collin. 

Fodere  observed  goiter  epidemics  in  Strassburg  and  says  that  sol- 
diers in  garrison  there  seldom  escape  goiter.  He  also  saw  an  epidemic 
in  the  Collegium  of  Strassburg  during  which  over  one-third  of  the  stu- 
dents developed  goiter.  According  to  Sigand,  goiter  suddenly  developed 
among  the  Brazilian  recruits  of  the  Rio  Urubez  (Goyaz)  with  such 
severity  that  the  recruits  were  seized  with  panic  and  deserted  to  their 
own  homes  in  the  Province  of  Para  where  their  goiters  rapidly  disap- 
peared.    Urubez  is  known  as  an  endemic  center. 

In  Neu  Breisach  between  the  years  1847-71  five  epidemics  are 
reported,  during  the  last  of  which  in  an  infantry  regiment  of  1002  men 
there  were  647  cases  of  goiter. 

In  the  year  1877,  during  an  epidemic  in  Belfort,  900  of  the  5300 
men  in  the  garrison  became  goiterous.  Seidlitz  reports  an  epidemic 
which  occurred  in  1877  when  the  Russian  troops,  during  the  war  with 
Turkestan,  occupied  the  city  of  Kokan;  of  the  2753  men,  245  became 
ill  with  goiter  and  the  condition  of  the  troops  became  so  alarming  that 
they  were  transferred  to  the  neighboring  city  of  Margelan  where  a 
satisfactory  amelioration  immediately  ensued. 

Hesse  observed  a  goiter  epidemic  in  the  school  of  non-commissioned 
officers  in  Manenberg,  Bavaria.  The  pupils  were  from  14  to  17  years 
of  age,  and  the  epidemic  was  attributed  to  the  tight  coat  collars,  this 
portion  of  the  uniform  often  becoming  too  small  because  of  the  rapid 
physical  development  due  to  the  youthful  age  of  the  pupils.  Goiter  is 
not  rare  in  the  population  of  Manenberg. 

In  Clermont-Ferrand  an  epidemic  is  reported  as  occurring  in  1812 
in  the  local  seminar}"  when  50  of  the  students  developed  goiters  within 
a  short  time.     Several  epidemics  of  goiter  occurred  in  the  barracks  of 


GOITER  EPIDEMICS  '  231 

Clermont-Ferrand  between  1843  and  i860.  In  1889  Augieras  observed 
in  Clermont-Ferrand  two  peculiarly  localized  foci — one  in  the  wing  of  a 
pavilion,  and  the  other  in  the  third  floor  of  a  barracks.  More  recent 
epidemics  are  reported  by  Costa  in  Drome,  by  Caljage  in  Finnland, 
occurring  in  an  otherwise  goiter-free  territory.  Cantemessa  in  Northern 
Italy  reports  an  epidemic  in  a  military  camp,  and  asserts  that  such  epi- 
demics not  infrequently  occur  among  soldiers  without  being  attributable 
to  drinking  water  or  to  soil  formation.  Cantemessa  attributes  these 
epidemics  to  infectious  conditions  due  to  extreme  summer-heat,  great 
fatigue,  and  lack  of  hygiene. 

Bottini  observed  an  epidemic  in  the  prison  of  Pallanza  when,  because 
of  reconstruction  of  one  of  the  wings  of  the  building,  the  prisoners  were 
crowded  together  in  the  remaining  part  of  the  prison;  after  cessation  of 
this  temporary  overcrowding  the  epidemic  disappeared. 

Numerous  goiter  epidemics  have  been  reported  in  boarding  schools 
and  educational  institutions  in  Lausanne,  in  Stuttgart,  etc.,  and  in  the 
Bishop  Cotton  School  in  Simla,  India.  Kutschera  reports  an  epidemic 
in  the  school-house  in  Goss  (endemic  territory).  The  headmaster,  his 
wife  and  six  children,  all  having  come  from  a  goiter-free  localitv,  acquired 
goiters  within  two  years  after  occupying  an  apartment  in  the  school- 
house.     In  1907,  60  per  cent,  of  the  children  of  the  school  wrere  goiterous. 

E.  Bircher  cites  an  interesting  observation  made  by  Cardinal  Billiet 
in  the  Normal  School  at  Albertville.  From  1840  to  i860  a  girls'  school 
occupied  the  buildings  and  goiter  was  unknown.  In  i860  architectural 
alterations  were  made,  and  the  rubbish  from  the  construction  was 
thrown  around  the  well.  The  buildings  then  passed  into  the  possession 
of  the  Normal  School  and  within  a  short  time  from  25  to  30  per  cent. 
of  the  pupils  became  goiterous.  Upon  replacing  the  well-water  by  rain- 
water for  drinking  purposes,  this  epidemic  entirely  disappeared. 

The  difference  between  epidemic  and  endemic  goiter  is  quantita- 
tive rather  than  qualitative,  the  same  conditions  and  deleterious  influ- 
ences being  the  cause  of  both.  The  fact  that  epidemics  usually  occur 
under  overcrowded  living  conditions  where  the  air  space  is  inadequate, 
has  led  McCarnson  to  suggest  that,  "Under  these  circumstances  the 
thyroid  gland  which  is  intimately  concerned  with  the  gaseous  exchanges 
of  the  body  may  be  abnormally  taxed,  and  the  addition  ol  goiterous 
influences  may,  by  making  a  further  demand  upon  its  functional  activ- 
ity, result  in  some  cases  in  its  visible  enlargement." 

I  hese  epidemics  in  most  cases  show  the  same  seasonal  fluctuation 
or  tendency  to  increase  during  the  summer  season  as  th<  endemic  dis- 
ease, hence  the  name,  "estiva!  goiter,"  or  "summer  goiter."  I  here 
seems  to  he  no  doubt  that  the  conditions  for  the  development  oi  goiter 
are  more  favorable  during  the  summer  months.     Nevet   says  that  the 


232  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

goiter  curve  in  Central  Europe  reaches  its  maximum  during  the  months 
of  May  and  June  and  McNamara  writes  of  Himalayan  India:  "It  is 
during  and  after  the  rains  that  the  disease  most  commonly  begins  and 
most  rapidly  develops."  This  seasonal  recrudescence  bears  some  anal- 
ogy to  typhoid  fever  and  to  other  infectious  diseases,  and  might  indicate 
pollution  of  the  water  supply  as  an  etiological  factor.  Some  authors 
attribute  this  increased  intensity  of  the  disease  during  the  warmer 
months  to  the  greater  quantity  of  drinking  water  consumed. 

FLUCTUATIONS    OF    ENDEMIC    GOITER. 

One  of  the  most  interesting  manifestations  of  this  enigmatical  dis- 
ease is  the  fluctuation  in  intensity  to  which  it  is  subject.  Whenever 
the  course  of  goiter  and  cretinism  has  been  studied  over  a  long  period 
of  time,  it  has  been  observed  that  the  disease  fluctuates,  sometimes  alter- 
nately increasing  and  declining,  sometimes  diminishing  persistently 
until  it  ultimately  disappears.  Or,  the  disease  may  augment  in  severity 
in  localities  where  the  endemic  has  been  mild,  and  even  makes  its  appear- 
ance where  it  was  formerly  unknown.  Again,  the  epidemic  may  disap- 
pear almost  entirely,  persisting  only  as  isolated  cases  which  are  then 
called,  "sporadic."  If  in  the  latter  localities,  epidemics  of  goiter  occur, 
they  are  usually  not  attributed  to  the  slight  persistent  endemicity  to 
which  they  are  really  due,  but  are  considered  as  of  sporadic  origin.  The 
goiterigenous  agent  seems  to  be  in  abeyance  rather  than  absent,  and  is 
apt  to  attack  susceptible  newcomers,  especially  if  living  under  non- 
hygienic  conditions,  or  if  crowded  into  buildings  and  sleeping  rooms 
with  inadequate  air  space,  as  soldiers  in  barracks,  or  children  in  boarding- 
schools  and  students  in  seminaries. 

James  Berry  has  truthfully  said  that,  "Most  goiters  may  be  consid- 
ered as  belonging  to  the  endemic  class,  but  the  endemicity  is  so  widely 
spread  over  the  whole  country,  while  at  the  same  time  it  is  so  slight  that 
it  escapes  notice,  and  cases  of  goiter  are  often  considered  as  sporadic 
which  should  more  correctly  be  classed  as  endemic."  Baillarger,  who 
studied  the  question  in  60  departments  of  France,  proved  conclusively 
that  between  the  years  1 830-1 865  the  endemic  had  increased  in  26 
departments,  had  diminished  in  17,  and  had  remained  stationary  in  the 
rest.  Fifteen  of  the  17  departments  in  which  he  found  goiter  diminish- 
ing, were  formerly  among  the  most  goiterous  of  the  whole  of  France. 
In  1880  Kocher  noticed  a  considerable  augmentation  of  goiter  in  certain 
parts  of  Germany  and  particularly  in  the  neighborhood  of  Berlin  (Berard). 
The  endemic  has  decreased  in  some  parts  of  Switzerland,  in  the  Pyrenees, 
in  the  Rhinelands,  in  the  Harz  Mountains,  in  Francoma,  and  in  Thunngia. 

Goiter  and  cretinism  have  disappeared  from  the  Island  of  Niederworth 


FLUCTUATIONS  OF  ENDEMIC  GOITER  233 

near  Coblentz  on  the  Rhine  where  the  endemic  was  formerly  so  intense 
that  few,  if  any,  of  the  inhabitants  escaped  goiter  or  some  of  its  sequelae. 
According  to  statistics  made  by  Cavatorti  in  1907,  goiter  has  completely 
disappeared  in  the  Italian  provinces  of  Ferrara,  Bara,  and  some  districts 
of  Sicily.  It  has  appreciably  diminished  in  Northern  Italy  which  was 
formerly  the  principal  center  of  endemicity  in  the  peninsula.  In  certain 
valleys  of  Spain  (Granada)  goiter  was  unknown  until  the  early  part  of 
the  last  century  when  it  first  appeared  and  spread  rapidly  over  a  wide 
area.  In  South  America  at  Manquita,  and  on  the  plateau  of  Bogota, 
the  number  of  goiters  declined  during  the  eighteenth,  and  increased 
again  in  the  nineteenth  century. 

McCarnson  cites  an  interesting  example  of  the  appearance  of  goiter 
in  a  locality  previously  exempt.  In  the  hill  state  of  Nagar  goiter  was 
unknown,  according  to  the  testimony  of  the  ruling  chief  and  principal 
dignitaries,  until  the  year  1898-99  when  4  goiterous  individuals  came 
to  reside  in  the  village  of  Nagar.  Three  of  these  individuals  were  mem- 
bers of  a  priest's  family  and  lived  in  a  house  close  to  the  head  of  a  spring 
supplying  the  village  with  drinking  water.  Six  years  later  McCarrison 
examined  the  inhabitants  of  Nagar  for  goiter  and  found  in  the  priest's 
family  seven  goiterous  individuals,  three  being  the  imported  cases, 
while  four  children  had  developed  the  disease  in  Nagar.  Since  the 
arrival  of  the  original  4  imported  cases  of  goiter,  18  cases  developed 
in  the  village  itself,  of  which  17  were  in  children  under  16  years  of  age. 
All  these  18  cases  came  from  a  part  of  the  village  supplied  by  the  spring 
at  the  head  of  which  lived  the  priest's  family. 

Two  years  subsequently  McCarrison  again  examined  the  inhabi- 
tants of  the  village  of  Nagar  and  found  13  new  cases  of  which  1 1  were  in 
children.  The  malady  did  not  spread  in  any  definite  line  nor  were  all 
of  the  children  in  the  same  house  always  affected. 

In  certain  districts  of  Brazil  (Natividad,  Rio  Grande  del  Sul)  goiter 
made  its  first  appearance  about  1830. 

Attention  is  drawn  to  the  etiological  value  of  these  observations  by 
Ewald  who  says,  "As  these  observations  have  been  authenticated  by 
reliable  investigators  and  are,  moreover,  of  so  simple  a  nature  that 
error  is  almost  excluded,  they  acquire  great  importance  for  the  etiology 
of  goiter,  as  they  show  that  the  primary  cause  of  the  disease  cannot  be 
a  permanent  and  unchanging  condition  inherent  in  the  locality  con- 
cerned, but  must  be  sought,  partially  at  least,  in  such  conditions  as  are 
subject  to  fluctuation,  sometimes  augmenting,  and  sometimes  declining." 

The  course  of  development  of  goiter  itself  is  fluctuating  in  the  incip- 
ient stage.  A  newcomer  to  a  goiterous  locality  may  acquire  an  enlarge- 
ment of  the  thyroid  gland  in  a  length  of  time  varying  from  eight  days 
to  three  months.      This  is  especially  true  of  foreign  travelers  who  come  to 


234  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

spend  the  summer  months  in  regions  where  goiter  is  endemic.  Often  this 
swelling  augments  rapidly  for  a  time  and  then  recedes,  remaining  station- 
ary, however,  before  the  gland  recovers  its  original  normal  condition. 
Now  unless  the  patient  is  removed  from  the  goiterigenous  influences,  the 
swelling  will  eventually  fluctuate  in  size  and  increase,  but  not  uniformly, 
sometimes  growing  with  the  seasonal  recrudescence  of  the  goiter  causa- 
tive factor,  sometimes,  augmenting  during  infectious  diseases  or  through 
some  other  cause.  Incipient  goiter  usually  disappears  spontaneously 
when  the  patient  leaves  the  endemic  territory,  but  if  again  subjected  to 
these  deleterious  influences,  hyperplasia  of  the  thyroid  gland  will  again 
ensue,  and  with  every  renewed  recurrence  the  gland  remains  larger 
than  before,  until  a  chronic  degenerative  process  results.  Thus  also 
with  the  goiter  of  pregnancy  when  frequently  recurring,  the  repeated 
hyperplasia  of  the  thyroid  gland  terminates  in  real  goiter. 

FLUCTUATIONS    OF   CRETINISM. 

Endemic  cretinism  is  subject  to  the  same  fluctuations  as  goiter. 
Ewald  states  that  in  the  German  Black  Forest,  in  the  Weserthal,  in 
Feldberg,  and  in  the  neighborhood  of  Homberg,  cretinism  has  died  out, 
although  there  has  been  no  change  in  the  water  supply  of  these  places. 

This  is  also  true  of  Freiburg  in  Breisgau  and  other  localities  where 
cretinism  has  disappeared,  and  where  the  water  supply  remained  the 
same.  Roesch,  writing  in  the  first  half  of  the  19th  century,  counts 
4967  cretins  in  Wiirttemberg,  and  mentions  districts  where  formerly 
there  was  little,  or  no  cretinism,  but  where  at  the  time  of  his  writing 
many  cretins  were  to  be  found.  Among  the  places  mentioned  by  Roesch 
are  Ergenzingen  where  in  1807  cretinism  was  unknown,  while  in  1847 
there  were  26  cretins.  In  Beinstein  and  Knitthngen  cretinism  had 
diminished,  while  in  OfFenau  and  Schutringen  it  had  augmented.  In 
Vachingen,  Stockheim,  and  Brachenheim,  endemic  cretinism  had  de- 
clined and  in  Giiglingen  it  had  alarmingly  increased,  etc.  In  Alt 
Oberndorf,  where  formerly  there  were  no  deaf-mutes  or  idiotic  individuals, 
Roesch  counted  36  cretins. 

At  the  present  time  cretinism  has  diminished  throughout  Wiirttem- 
berg. 

Kutschera  reports  concerning  the  fluctuation  of  cretinism  in  Styria 
as  follows:  in  1861  in  a  population  of  978,785  there  were  5856  cretins, 
i.  e.,  1  cretin  to  167  inhabitants;  at  the  present  time  there  are  2517 
cretins,  or  1  to  every  539  inhabitants. 

Graz  and  the  district  of  Maria  Zell,  where  formerly  cretinism  pre- 
vailed, are  now  free  from  the  cretinoid  degeneration.  Formerly  in  the 
district  of  Oberwolz  there  was  1  cretin  to  24  inhabitants,  and  the  dis- 


FLUCTUATIONS  OF  CRETINISM  235 

trict  of  St.  Gallen  was  without  cretinism.  These  conditions  are  now 
reversed.  The  district  of  Oberwolz  is  now  cretin-free,  but  in  the  district 
of  St.  Gallen  cretinism  is  widely  distributed.  In  the  district  of  Neu- 
markt,  where  endemic  cretinism  was  formerly  intense,  it  has  diminished 
remarkably,  whereas  in  the  districts  of  Oberzeiring  and  Judenburg  it 
has  greatly  increased. 

In  the  Paltental  endemic  cretinism  has  disappeared  from  many 
places  and  remained  stationary  in  others. 

Not  only  does  the  disease  fluctuate  in  endemic  area,  but  the  degree 
of  endemicity  also  varies  greatly  between  different  adjacent  villages  and 
even  in  different  parts  of  the  same  village.  St.  Lager  tells  of  the  village 
Antignano  (Asti)  which  drew  its  water  supply  from  three  wells.  The 
families  using  the  first  well  suffer  from  both  goiter  and  cretinism,  those 
using  the  second  are  only  goiterous,  and  those  who  drink  water  from 
the  third  well  are  entirely  free  from  both  diseases. 

Kutschera  mentions  the  village  of  Lassing  in  the  district  of  Liezen, 
consisting  of  five  peasant  houses,  all  of  which  had  the  same  water  sup- 
ply and  where  the  conditions  of  life  were  identical,  yet  in  one  of  these 
houses  there  were  many  cases  of  cretinism,  while  the  inhabitants  of  the 
other  houses  remained  exempt. 

McNamara  states  that,  "In  villages  situated  along  the  banks  of  the 
Ravi  which  are  subject  to  the  same  telluric,  atmospheric,  and  hygienic 
conditions,  the  difference  in  the  endemicity  of  goiter  in  villages  quite 
close  together  was  remarkable." 

Bircher  reports  that  cretins  and  deaf-mutes  are  numerous  on  the 
right  bank  of  the  River  Aare,  while  the  left  bank  is  completely  free  from 
cretinism. 

Conclusions  Drawn  from  the  Study  of  the  Fluctuations  of  Goiter  and 
Cretinism. — On  the  whole  endemic  goiter  seems  to  be  diminishing  inten- 
sively if  not  extensively.  The  large,  degenerated  goiters,  often  accom- 
panied by  myxedematous  complications,  which  were  formerly  frequently 
encountered  in  endemic  centers  are  rarely  seen  now,  and  there  can  be 
no  doubt  that  the  cretinoid  degeneration  has  sensibly  decreased  both 
in  frequency  and  in  area  of  distribution.  It  seems  probable,  after  exam- 
ining all  the  statistics  before  us,  that  the  total  number  of  goiter-bearers 
has  not  greatly  altered,  but  that  these  goiters  remain  small,  that  their 
symptoms  are  less  severe,  and  that  their  dread  sequela?  of  cretinism 
and  deaf-mutism  occur  less  frequently. 

This  decline  in  the  severity  of  the  manifestation  of  the  disease  is 
probably  due  to  several  factors  such  as  the  general  increase  in  well- 
being,  improved  hygienic  conditions,  and  to  the  fact  that  the  population 
is  no  longer  a  fixed  and  unchanging  product  of  the  endemic  locality  .is 
formerly. 


236  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

Under  modern  conditions  of  life  the  peasant  frequently  emigrates 
or  moves  to  the  city,  and  his  place  is  taken  by  a  newcomer  often  from 
immune  territory,  so  that  opportunity  for  the  accumulated  toxic  effect 
of  the  goiter  poison  upon  successive  generations  is  far  less  frequent  than 
of  old. 

Nor  must  it  be  forgotten  that  the  surgical  treatment  of  goiter  has 
done  much  toward  preventing  the  monstrous  deformity  which  was 
formerly  so  familiar  a  sight  in  regions  of  severe  endemicity. 

At  present  when  a  goiter  commences  to  assume  such  proportions  as 
to  cause  inconvenience,  or  disfigurement,  the  case  is  given  medical 
treatment,  and  if  this  fails  to  arrest  the  development  of  the  disease, 
recourse  is  had  to  surgical  intervention,  from  which  the  best  and  most 
permanent  cures  known  to  us  have  been  obtained. 

GOITER   IN    ANIMALS. 

As  we  have  already  seen,  animals  in  endemic  territory  suffer  from 
goiter  as  well  as  man.  Vegetius  (4th  century)  observed  goiter  in  draft 
animals,  and  mentions  struma  as  well  as  swellings  of  the  parotid  gland 
and  scrofulous  tumors  in  his  "Ars  Veterinaria  sive  Mulomedicina" — 
"Plerumque  strumae,  vel  parotides,  aut  scrophulae  jumentorum  guttur 
infestant  et  faucium  tumorem  producunt."  Classic  writers  report  lions 
as  goiterous  in  a  certain  portion  of  the  Mediterranean  Coast,  in  the 
Atlas  Mountains,  where  the  existence  of  the  endemic  was  recognized 
by  the  ancients.  The  Berber  traveler,  Leo  Africanus,  wrote  of  the  lions 
of  Morocco  in  the  latter,  part  of  the  15th  century,  that  they  were  both 
goiterous  and  cowardly,  a  statement  which  explains  the  old  proverb, 
"Thou  art  brave  as  a  lion  of  Agla  whose  tail  may  be  eaten  by  calves." 
In  modern  times  observations  and  investigations  concerning  goiter 
among  animals  have  become  more  and  more  frequent  with  the  growing 
realization  that  the  factors  responsible  for  the  degenerative  process  in 
man  occasion  similar  results  in  the  animal  kingdom.  I  am  now  speak- 
ing of  endemic  influences  upon  animals  under  natural  conditions.  Later 
I  shall  refer  to  the  valuable  experimental  work  upon  animals  to  which 
we  owe  much  of  the  little  knowledge  we  possess  on  this  subject.  Goi- 
terous dogs  and  pigs  were  observed  by  Kaissler  in  the  Valley  of  Aosta, 
and  by  Fodere  in  the  Maurienne,  while  Rougieux  and  Tallard  observed 
them  in  the  Department  of  Meurthe,  Verdeil  in  the  Canton  of  Vaud, 
Schneider  in  the  Canton  of  Berne,  Roesch  in  Wiirttemberg,  Guerdan  in 
the  Grand-Duchy  of  Baden,  and  Mollien  in  New  Granada  (Columbia). 
Campbell  and  Bramley  report  the  finding  of  goiterous  dogs  on  the  slopes 
of  the  Himalayas,  and  McClelland  saw  goiterous  dogs  and  cats  on  the 
banks  of  the  Gunduk,  a  tributary  of  the  Ganges. 


GOITER  IN  ANIMALS  237 

Goiter  has  been  found  among  cattle  and  sheep  in  the  Auvergne,  in 
the  Jura,  in  Switzerland,  in  Baden,  in  Wiirttemberg,  in  the  Danube 
Valley,  in  Piedmont,  in  Siberia,  and  in  Brazil.  In  the  valley  of  the 
Gunduk  where  McClelland  found  goiterous  dogs  and  cats,  Campbell 
observed  this  disease  among  sheep  and  goats.  Bramlev  saw  goiter 
among  camels  in  Purneah.  An  observation  of  Gustave  Radde's  which 
Bircher  cites,1  is  especially  interesting,  as  it  shows  that  goiter  exists  in 
wild  animals  as  well  as  among  their  domesticated  brothers.  In  the  dis- 
trict of  Nertschinsk,  in  Siberia  near  the  Chinese  frontier,  Radde  encoun- 
tered a  goiterous  antelope  which  he  called  "antilope  gutturosa."  South 
of  the  Baikal-Sea  he  did  not  find  this  goiterous  species,  and  it  is  exceed- 
ingly probable  that  what  he  considered  a  natural  species  of  antelope 
was  merely  a  pathological  product,  since  in  the  region  inhabited  bv 
these  animals  endemic  goiter  prevails,  while  it  is  absent  south  of  the 
Baikal-Sea. 

Russian  physicians  have  observed  goiter  among  horses  in  the  same 
regions  of  Siberia  where  Radde  found  the  goiterous  antelope,  and  also 
in  the  Government  of  Olonetz.  It  occurs  among  horses  in  Guatemala, 
in  the  United  States,  in  Brazil,  in  the  Argentine  Republic,  in  Carinthia, 
in  the  Valley  ot  Aosta,  in  the  Department  of  Meurthe,  and  according  to 
Mayor  and  Vicat,  in  the  Canton  of  Geneva. 

Baillarger  reports  the  frequent  rinding  of  goiter  among  mules  in  the 
Maunenne  and  Modena;  in  the  latter  locality  he  found  19  goiterous  mules 
in  a  stable  of  20;  while  Peronnet  and  Lecoq  saw  in  Savoy  28  goiterous 
mules  among  60,  and  among  45  horses  15  had  goiters.  Pellat  in 
Allevard  near  Grenoble  reports  that  out  of  55  mules  examined  bv  him 
47  had  goiters.  According  to  Baillarger,  in  the  stables  of  the  gendar- 
merie at  St.  Jean  du  Maunenne  4  out  of  7  horses  became  goiterous  within 
less  than  two  years.  Raynard  and  Rougieux  maintain  that  they  have 
observed  a  decline  of  intelligence  in  horses  and  dogs  suffering  from 
goiter.  We  have  ahead)'  mentioned  Marine's  report  of  the  wide  dis- 
semination of  goiter  among  animals  along  the  Great  Lakes  of  North 
America.  He  affirms  that  90  per  cent,  of  the  street  dogs  of  Cleveland 
show  some  degree  of  hyperplasia  of  the  thyroid  gland,  and  in  some  casts 
actual  colloid  goiter.  He  considers  this  hyperplasia  as  an  indubitable 
indication  of  goiterous  influences.  In  well-cared  for  dogs  there  is  a 
lesser  degree  of  the  thyroid  hyperplasia.  Marine  further  finds  that  90 
per  cent,  of  the  sheep  on  Lake  Erie  show  some  enlargement  of  the  thy- 
roid gland  and  that  the  cattle  are  affected  in  a  lesser  degree.  He  records 
that  in    Michigan   twenty  years  ago   the  sheep   industry   suffered   a   set- 

1   I'lie  greater  part  of  these  preceding  observations  concerning  animals  is  cited  from 
H.  Bircher. 


238  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

back  on  account  of  the  number  of  cretin  lambs  born,  but  today  this 
condition  is  gradually  disappearing  owing  to  acclimatization,  or  per- 
haps to  the  development  of  a  natural  resistance  to  the  disease,  but 
especially  to  the  use  of  iodin-containing  salt.  Marine  reports  the  occur- 
rence of  goiter  among  fish  in  endemic  localities  and  says  that  carnivorous 
fish  only  are  affected  under  natural  conditions.  Artificially  bred  trout 
are  peculiarly  liable  to  this  disease.  Gaylord,  of  Buffalo,  has  made  very 
interesting  observations  concerning  goiter  epidemics  among  fish.  The 
fish  tanks  that  he  described  were  located  one  above  the  other,  and  fed 
from  the  same  stream  flowing  from  one  tank  into  the  next,  from  above 
downward.  In  the  first  tank  the  fish  were  3  per  cent,  goiterous;  in  the 
second,  8  per  cent.;  in  the  third,  45  per  cent.;  and  in  the  fourth,  85 
per  cent. 

In  the  stream  above  the  tanks  the  transplanted  fish  remained  healthy, 
from  which  circumstance  Plehn  draws  the  conclusion  that  the  nox- 
ious agent  is  not  contained  in  the  water,  but  in  the  bed  of  the  tank 
whence  it  passes  down  the  stream  in  accumulating  quantities.  Kuts- 
chera  considers  that  these  observations  clearly  prove  that  the  goiter 
agent  is  not  conveyed  by  the  water  itself,  but  that  it  is  transmitted  by 
contact  in  the  water.  If  that  is  the  case,  it  is  difficult  to  understand 
why  the  fish  in  the  stream  below  the  tanks  should  escape  the  infection 
as  is  reported  by  Marine  and  Lenhardt,  farther  on  in  the  present  treatise. 

The  similarity  of  fish-goiter  with  that  of  warm-blooded  animals  is 
not  only  histologically  established,  but  is  also  further  confirmed  by 
Gaylord's  experiment  in  giving  dogs  and  rats  water  to  drink  from  these 
goiter  tanks,  when  as  a  result  they  frequently  developed  an  enlargement 
of  the  thyroid  gland. 

Another  observation  of  Gaylord  would  seem  to  speak  in  favor  of 
the  parasitic  origin  of  goiter.  Upon  the  addition  of  an  infinitesimal 
quantity  of  antiseptic  such  as  sublimate  or  potassium  iodide  (solution 
of  1.5  milhonths)  to  the  tanks,  a  slow  but  unmistakable  retrogression  in 
the  fish-goiter  occurred.  When  the  goiterous  fish  were  transferred  into 
different  waters,  the  goiter  disappeared,  and  even  in  the  infected  tanks, 
some  trout  recovered  spontaneously  and  developed  complete  immunity 
from  the  injurious  influence  of  the  goiter  agent. 

The  following  observations  of  Drs.  Marine  and  Lenhardt  were  made 
in  a  private  hatchery  in  the  mountains  of  Pennsylvania  during  the 
months  of  October  and  November,  1909.  The  fish  tanks  in  question 
were  arranged  in  a  single  series  down  the  course  of  the  brook,  each 
house  containing  several  tanks.  A  single  spring  supplied  the  six  upper 
houses,  while  the  lower  five  received  the  water  that  had  passed  through 
the  upper  six,  together  with  that  from  a  second  small  spring,  and  a  six- 
inch  pipe  line  from  a  large  stream  about  a  quarter  of  a  mile  to  the  left. 


GOITER  IN  ANIMALS  239 

Between  houses  6  and  7  the  water  followed  the  original  brook  for  a 
quarter  of  a  mile,  then  it  was  again  collected  bv  means  of  a  dam  and 
entered  the  lower  division  commencing  with  house  7,  with  the  addition 
to  its  volume  above  mentioned,  otherwise  the  water  was  carried  in  cov- 
ered race-ways  made  of  lumber.  As  a  result  of  the  examination  of  the 
fish  contained  in  these  different  tanks  and  houses  and  in  the  race-wavs 
above  and  below  all  houses,  the  authors  conclude  that:  "Fish  from  the 
race-way  above  all  houses,  and  which  have  never  been  confined  to  the 
tanks,  maintain  normal  thyroids  throughout  their  lives,  but  beginning 
with  the  uppermost  tank  the  fish  are  markedlv  affected  and  there  is  a 
gradual  increase  in  the  degree  of  thyroid  proliferation  which  reaches  its 
maximum  in  house  6,  the  last  of  the  upper  series.  Beginning  with 
house  7  there  is  a  marked  improvement  and  lessening  of  the  active 
thyroid  proliferation  coincident  with  the  greatlv  increased  water  supply 
and  the  probable  purification  of  the  water  in  its  passage  from  house  6 
to  7  along  the  original  bed  of  the  brook."  The  examination  of  the  fish 
from  the  tail-race,  living  wild  but  in  the  polluted  water,  showed  their 
thyroids  to  be  normal  in  type.  Examination  of  the  older  fish  that  were 
removed  from  the  tanks  into  the  larger  stream  indicated  that,  although 
the  thyroid  tissue  had  invaded  all  the  structures  beneath  the  pharvngeal 
mucosa  at  some  past  period  of  their  lives,  nevertheless,  their  stay  of  from 
five  to  six  months  in  a  natural  environment  afforded  a  complete  relief, 
so  that  the  thyroids  resumed  their  resting  or  colloid  state.  The  authors 
conclude  that  "overfeeding  or  overcrowding,  and  a  limited  supplv  of 
water  produce  filthy  unhygienic  tanks  and  such  tanks  are  in  a  very 
important  but  still  unknown  way  associated  with  thyroid  hyperplasia." 

It  is  interesting  to  note  that  trout  also  conform  to  that  striking 
characteristic  of  endemic  goiter,  viz.,  the  capacity  for  spontaneous 
recovery  on  removal  from  the  infected  area.  The  markedly  place- 
character  of  the  disease  even  in  the  case  of  these  fish  is  thus  illustrated 
(McCarrison). 

Nevertheless,  as  a  whole,  goiter  and  cretinism  are  less  frequent  in 
animals  than  in  human  beings,  and  it  should  not  be  forgotten  in  forming 
conclusions  based  upon  animal  experiments,  that  they  possess  a  greater 
degree  of  resistance  to  the  goiter  agent  than  exists  in  man.  Animals 
may  remain  immune  from  goiter  in  the  regions  where  the  endemic  pre- 
vails among  human  beings.  The  domestic  water-drinking  animals  are 
much  more  subject  to  goiter  than  those  which  obtain  their  provision 
of  water  from  green  food.  Thus,  it  is  extremely  difficult  to  produce 
goiter  experimentally,  for  example,  in  rabbits,  guinea-pigs  and  monkeys. 

McCarrison  reports  from  the  districts  of  Chitral  and  Gilgit  in  the 
Western  Himalayas,  where  the  endemic  is  most  intense,  that  among 
567  animals  examined  h\    him  he  did  not  encounter  one  ease  of  the  dis- 


240  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

ease.  In  one  village  where  45  per  cent,  of  the  male  population  were 
goiterous  he  examined  all  the  dogs  without  finding  a  single  animal  that 
showed  enlargement  of  the  thyroid  gland.  This  is  in  direct  opposition 
to  the  observations  of  Adam  whose  notes  upon  goiter  endemics  among 
animals  in  the  territory  of  Augsburg  and  along  the  River  Lech  show  that 
these  endemics  are  coincident  with  the  malady  among  human  beings, 
the  endemic  area  for  human  beings  and  animals  alike  being  confined  to 
the  left  bank  of  the  river. 

Adam  reports  a  goiter  endemic  observed  by  him  among  horses  in 
Augsburg.  In  certain  stables  in  the  east  and  northeast  portion  of 
Augsburg,  newlv  imported  horses  from  immune  territory  acquired  a 
swelling  of  the  thyroid  gland  which  receded  upon  the  application  of 
iodin.  All  of  these  stables  lay  upon  the  left  bank  of  the  river  Lech, 
while  horses  stabled  in  the  west  side  of  the  city  did  not  surfer  from  goiter. 
Adam  further  states  that  not  all  the  horses  in  the  affected  stables  acquired 
goiter,  about  one-half  of  each  new  lot  remaining  exempt  so  that  a  cer- 
tain predisposition  must  exist  among  them  as  among  human  beings. 
Adam  cites  the  observation  of  the  veterinary  surgeon,  Mussgnug,  that 
in  the  whole  territory  of  Augsburg  goiter  prevails  among  animals  on 
the  left  side  of  the  river  Lech  and  not  on  the  right  side. 

Adam  further  observes  that  among  very  young  dogs  marked  swelling 
of  the  thyroid  gland  is  frequently  observed,  but  that  this  goiter  usually 
disappears  as  the  dog  acquires  its  growth. 

Schittenhelm  and  Weichardt  remark  that  this  coincides  with  the 
predominance  of  thyroid  enlargements  among  children  in  endemic  terri- 
tory which,  according  to  Kocher,  attains  90  per  cent.,  reaching  its  maxi- 
mum at  about  the  tenth  year,  and  then  retrogressing.  Berard  cites  an 
observation  reported  to  him  by  Dr.  Furet,  of  Brides,  who  brought  a 
bitch  from  Geneva  to  Brides  where  the  animal  acquired  goiter.  The 
following  year  she  gave  birth  to  several  puppies,  one  of  which  was  born 
with  a  thyroid  tumor.  This  goitrous  puppy  was  seriously  retarded  in 
his  development;  he  was  very  slow  in  learning  to  eat  alone,  did  not 
understand  when  called,  and  finally  allowed  himself  to  be  run  over  and 
killed  by  a  wagon  of  which  the  horse  was  advancing  at  a  walk. 

It  is  interesting  to  observe  that  in  endemic  goiter  among  animals 
the  influence  of  individual  predisposition,  sex,  and  hygienic  living  seems 
to  be  the  same  as  in  man.  In  groups  of  animals  under  precisely  the 
same  conditions  and  exposed  to  the  same  toxic  influences  some  will 
develop  goiter  and  others  will  remain  immune,  as  is  clearly  demonstrated 
in  all  of  the  endemics  occurring  among  horses  and  mules  in  certain 
stables. 

Goiter  occurs  more  frequently  in  the  female  sex  among  animals,  just 
as  is  the  case  in  human  beings,  and  this  disparity  decreases  in  propor- 


THEORIES  REGARDING  THE  ETIOLOGY  OF  GOITER  241 

tion  as  the  endemic  increases  in  intensity.  And  furthermore,  from 
Marine's  observation  that  goiter  is  less  frequent  among  well-cared-for 
dogs  than  among  neglected  ones,  it  would  seem  that  general  well-being 
augments  the  individual  power  of  resistance  in  animals  as  in  man  to  the 
endemic  process. 

THEORIES    REGARDING    THE    ETIOLOGY   OF   GOITER. 

The  various  theories  as  to  the  etiology  of  goiter  may  be  divided  into 
two  groups : 

i.  That  of  the  exogenous  j actors. 
2.  That  of  the  endogenous  j  actors. 

Among  the  exogenous  factors  is  included  the  greater  part  of  those 
numerous  and  diverse  theories  which  have  sprung  up  around  this  ques- 
tion, induced  by  the  luxuriant  fertility  of  the  imagination  rather  than 
attained  through  the  slow  and  cautious  development  of  a  scientific 
process. 

St.  Lager  cites  378  authors  and  42  different  opinions,  some  of  which, 
such  as  the  influence  of  weather,  light,  temperature,  racial  conditions, 
mechanical  injuries,  configuration  of  the  soil,  etc.,  are  evidently  unten- 
able because  of  the  wide  distribution  of  goiter. 

A  causal  influence  has  been  attributed  by  Saussure  to  want  of  sun- 
shine and  to  lack  of  renewal  of  the  air  in  the  deep-laid  mountain  vallevs; 
by  Gosse,  and  more  recently  by  Chopinet,  to  the  humidity  of  the  soil; 
by  Lizzoli  to  air  containing  too  much  oxygen;  by  Fodere  and  Niepce 
to  climatic  conditions.  Heidenreich  attributes  to  the  moon  an  influence 
upon  the  thyroid  gland.  Various  conditions  of  the  atmosphere  have 
been  incriminated,  such  as  air  charged  with  sulphurous  vapors,  or  elec- 
tricity, or  air  wanting  in  iodin,  or  air  that  is  too  cold  or  too  dry,  and 
so  forth. 

Social  and  economic  conditions  have  been  considered  the  cause  of 
goiter  by  many  French  and  Italian  writers.  But  the  evidence  before 
us  seems  to  establish  definitely  that  all  social  classes  and  conditions  suffer 
from  goiter.  Neither  the  rich  nor  the  poor  enjoy  a  special  immunity, 
although  there  would  seem  to  be  some  relation  between  occupation  and 
the  development  of  goiter  since  the  mining  and  agricultural  classes  in 
endemic  territory  are  more  subject  to  the  disease  than  others.  This 
fact  suggests  that  the  close  contact  of  these  laborers  with  the  soil  might 
be  an  etiological  factor. 

Hanshalter   and   Jeandelize   observed    a    considerable   diminution    in 
the    intensity    of   the    endemic    in    that  ancient   goiter   center    Rosieres 
Department  of  Meurthe  et    Moselle,   after  the   introduction   ot   water- 
works  and   improved  sanitary  conditions,   and   therefore  concluded   that 
16 


242  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

besides  the  microorganisms,  hygienic  conditions  play    a    predominating 
role  in  the  etiology  of  the  disease  (loc.  at.,  Bircher). 

Some  authors  have  attributed  an  etiological  influence  to  the  habit 
of  bearing  burdens  upon  the  head,  but,  as  this  custom  is  confined  to 
narrow  territorial  limitations,  while  goiter  is  as  widespread  as  the  inhab- 
ited earth,  this  theory  is  evidently  false.  The  very  wealth  of  publica- 
tions and  hypotheses  on  the  subject  renders  the  necessary  selection  and 
elimination  an  exceedingly  difficult  and  perplexing  process.  The  greatest 
criticism  that  can  be  made  of  most  of  the  theories  advanced  is  that  they 
have  been  elaborated  to  fit  certain  circumscribed  areas  only.  They  are 
thus  rendered  valueless,  as  they  do  not  grasp  the  problem  as  a  whole, 
but  discuss  some  phases  of  it  only.  Consequently  it  becomes  neces- 
sary to  read,  weigh,  and  compare  all  of  these  diverse  views,  seeking  the 
connecting  link  where  scientifically  established  facts  are  recorded,  and 
setting  aside  such  evidence  as  is  purely  circumstantial.  In  all  the  liter- 
ature concerning  goiter  which  has  come  down  to  us  throughout  the  ages 
there  is  but  one  conclusion  which  is  constantly  and  predominatingly 
present,  i.  e.,  the  relation  existing  between  water  and  endemic  goiter. 

The  Relation  between  Water  and  Endemic  Goiter. — This  relation  has 
been  popularly  accepted  from  the  earliest  times,  and  among  the  ancients 
certain  springs,  wells,  and  rivers  were  reputed  as  goiterigenous  and  their 
water  avoided  for  drinking  purposes.  As,  for  example,  in  Chios  where 
an  inscription  was  placed  above  a  well  warning  the  thirsty  passerby 
that  this  water  rendered  those  who  drank  of  it  dull.  Another  such  well 
existed  in  Beotia,  near  the  River  Orchomenes,  and  was  believed  to 
cause  loss  of  memory;  likewise  the  Red-well  in  Ethiopia  and  the  Gallus 
River  in  Phrygia  were  supposed  to  affect  the  mind.  Ovid  said,  ". 
sunt  qui  non  corpora  tantum  verum  etiam  ammos  valiant  mutare 
liquores."  Hippocrates,  Aristotle,  Galien,  Celsus,  and  Pliny  discuss  at 
length  the  mysterious  virtue  and  power  of  these  strumigenous  springs 
and  mention  those  of  the  Apennines,  of  Phrygia,  of  Chios,  and  Crete. 
Vitruvius  wrote  of  the  people  inhabiting  the  Maurienne  valley  where 
the  endemic  prevails  with  intensity  to  this  day:  "Acquiculus  in  Italia 
et  Alpibus,  nationi  Medullorum  est  genus  aquae,  quam  qui  bibunt 
efficiuntur  turgidis  gutturibus."  Agricola,  1546,  notes  a  well  in  Coire, 
"Cujus  aquae  potae  adeo  laedunt  cerebrum  ut  stohdos  faciant,"  and  as 
early  as  1574  Josias  Simler  in  the  Canton  of  Valais,  and  Felix  Platner 
in  16 14  in  Bale,  endeavored  to  establish  clearly  the  relationship  already 
perceived  by  the  ancients  between  certain  waters  and  some  kinds  of 
tumor  of  the  throat,  often  associated  with  a  form  of  degeneration  where 
idiocy  and  arrested  physical  development  were  combined.  In  1680 
J.  Wagner,  in  Article  18  of  his  Natural  History,  enumerates  the  goiter- 
wells  in  the  Cantons  of  Berne,  Grisons,  etc.,  among  which  he  mentions 


THEORIES  REGARDIXG  THE  ETIOLOGY  OF  GOITER  243 

Fons  Regis  of  Berne.  In  more  modern  times  the  goiterigenous  proper- 
ties of  certain  wells  were  so  generally  accepted  that  young  men  liable 
to  military  service  drank  of  these  waters  in  order  to  acquire  goiter  and 
thus  to  escape  military  duty.  These  facts  are  reported  concerning  wells 
in  Argentine,  Pantamafrev,  \  lllard-Clement,  St.  ChafFrev,  and  Cava- 
curta  in  Lombardy,  of  which  last  Lombroso  writes,  "La  fonte  del  gozzo 
ove  soghono  andare  1  giovani  all  epoca  della  coscnzione  onde  acquistare 
in  qumdici  giorni  quel  difetto  che  li  sostrae  dal  servizio."  (The  goiter- 
fountain  which  is  visited  by  youths  at  the  time  of  conscription  in  order 
to  acquire  this  infirmity  in  two  weeks,  and  thus  avoid  military  service.) 
In  reference  to  this  well,  it  must  be  said,  however,  that  Kutschera 
quotes  Grassi  and  Munaron  as  having  examined  the  well  and  as  having 
established  the  fact  that  no  one  in  Cavacurta  knew  of  its  possessing  the 
injurious  properties  attributed  to  it,  and  further,  that  goiter  has  never 
been  endemic  in  this  locality.  In  connection  with  these  findings  of  Grassi 
and  Munaron  we  might  recall  that  St.  Lager  affirms  that  the  authen- 
ticity of  these  statements  was  investigated  by  him  personally  and  con- 
firmed by  the  testimony  of  reliable  persons  such  as  priests,  doctors,  and 
magistrates. 

We  can,  I  thmk,  accept  as  an  established  fact  that  the  goiter  causa- 
tive factor,  whatever  its  nature  may  be,  is  most  frequently  conveyed 
to  the  human  organism  through  drinking  water.  The  general  consensus 
of  opinion  among  investigators  concurs  in  this  point,  although  differing 
in  all  other  things.  The  most  convincing  proof  in  support  of  the  infec- 
tion of  drinking  water  is  furnished  by  the  many  reliably  observed  and 
recorded  cases  of  individuals,  newcomers  from  goiter-free  territory  to 
the  endemic  area,  who  rapidly  acquired  hyperplasia  of  the  thyroid 
gland  after  drinking  the  water  from  these  goiterigenous  wells,  and  whose 
swelling  as  rapidly  subsided  after  they  ceased  the  use  of  the  water. 
Many  of  these  epidemics  already  mentioned  seem  to  be  collective  experi- 
ments in  this  sense:  and  merely  deserve  the  name  epidemic  because 
occurring  in  groups  instead  of  in  individual  cases,  from  which  they  differ 
in  no  other  respect. 

Many  instances  are  recorded  where  boiling  the  drinking  water  suf- 
ficed to  prevent  the  occurrence  of  goiter  in  endemic  territory  as  in  the 
case,  reported  by  Breitner,  of  a  railroad  line-keeper's  family  where 
father,  mother,  and  seven  children,  all  acquired  enlargements  of  the 
thyroid  gland  upon  drinking  water  horn  a  goiter  well.  Breitner  advised 
boiling  the  water  before  using  it  and  within  four  weeks  the  swellings 
had  visibly  diminished.  Later,  this  family  again  drank  the  unboiled 
well  water  and  the  swellings  at  once  recurred.  Numerous  cases  are 
recorded  where  the  use  of  rain  water  was  sufficient  protection  against 
the  endemic  disease.     Dr.  Mottard  cites  the  case  of  a  citizen  ot  Bourieux, 


244  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

Maurienne,  who  constricted  a  cistern  for  rain  water  and  thus  preserved 
his  family  and  neighbors  immune  in  the  midst  of  the  endemic,  by  the 
exclusive  use  of  this  water. 

Billiet  and  Boussingault  report  similar  cases.  Mgr.  Billiet  knew  of 
but  one  family  in  Planaise  exempt  from  goiter,  and  in  this  household 
rain-water  was  used  exclusively  for  drinking  purposes.  Baillarger  reports 
a  case  observed  by  Dr.  Housseaut  in  Grozon  where  the  railroad  employees 
acquired  goiter  within  a  short  time  after  their  arrival  in  endemic  territory. 
In  answer  to  their  complaints  the  railroad  company  built  a  cistern  and 
from  this  time  on  the  employees  remained  free  from  goiter. 

Further  observations  as  to  the  immunity  of  rain  water  from  the 
goiter  agent  have  been  made  by  Kocher,  E.  Bircher,  and  others.  Of 
special  significance  is  the  case  observed  by  Dr.  Gauthier  in  Fort  de 
l'Ecluse  and  reported  by  H.  Bircher.  The  garrison  of  the  upper  fort 
drew  their  drinking  water  from  a  cistern  and  were  free  from  goiter, 
whereas  the  lower  fort  used  spring  water  and  goiter  became  prevalent 
among  the  troops. 

John  W.  McClelland  reports  an  endemic  in  Deoba,  India  ("Some 
Inquiries  in  the  Province  of  Kemaon  Relative  to  Geology  Including  an 
Inquiry  into  the  Causes  of  Goiter,"  1835,  printed  in  Dublin  Jour,  of  Med. 
Science,  11,  295,  1837),  which  is  of  special  importance  for  the  drinking- 
water  theory  of  the  etiology  of  goiter.  The  Brahmins  or  highest  caste 
of  the  population  were  entirely  free  from  the  prevailing  endemic,  their 
water  supply  being  brought  in  pipes  from  a  distant  spring,  and  to  this 
supply  the  other  classes  had  but  partial  or  no  access. 

The  middle  caste  (Rajputs)  drank  partly  good  and  partly 
goiterigenous  water,  and  were  two-thirds  goiterous,  while  the  lowest 
class  (Domes),  who  were  dependent  for  their  entire  water  provision 
upon  the  local  goiterigenous  springs  were  goiterous  throughout.  Kuts- 
chera,  however,  considers  this  case  as  a  proof  of  the  infection  by  contact 
theory,  and  explains  the  upper  caste's  exemption  from  the  endemic  not 
because  of  the  use  of  different  water,  but  rather  in  the  complete  separa- 
tion and  isolation  of  the  Brahmins  from  the  infected  lower  castes. 

The  peculiar  and  interesting  conditions  of  the  endemic  in  the  village 
of  Antignano  have  already  been  mentioned,  where  of  the  three  wells 
used  by  the  inhabitants,  one  caused  goiter,  the  second  goiter  and  cretin- 
ism, while  the  third  was  free  from  both  deleterious  influences.  Avillard 
suffers  only  in  winter  from  goiter  while  using  well  water,  and  the  disease 
ceases  during  the  summer  when  the  inhabitants  drink  snow  water. 

When  in  Longematte  (Savoy)  the  spring-water  supply  was  cut  off, 
and  it  became  necessary  to  sink  wells,  goiter  immediately  ensued. 

Humboldt  reports  from  Colombia  that  until  1870  there  was  no  goiter 
in  Maraquita  and  the  plateau  of  Bogota,  while  the  disease  was  endemic 


THEORIES  REGARDING  THE  ETIOLOGY  OF  GOITER 


245 


in  the  rest  of  the  Magdalena  Valley;  up  to  that  time  the  population  of 
this  goiter-free  region  drank  only  river  water  and  it  was  not  until 
well  water  came  into  use  that  goiter  occurred.  It  has  been  observed 
that  goiter  may  be  produced  or  eliminated  by  a  mere  change  in  the 
location  of  wells,  as  in  the  case  of  Saillans  and  Saxon  in  Yalais,  and 
Nozeroy  (Jura).  On  the  other  hand,  in  Nottingham  goiter  appeared 
when  it  became  necessary  to  sink  the  already  existing  wells  deeper. 

Numerous  authors  have  cited  examples  of  rivers  and  streams,  which, 
although  goiterigenous  at  their  source,  lose  this  property  during  their 
course,  and  vice  versa,  streams  which  were  innocuous  originally  may 
become  infected  during  their  course,  probably  through  the  addition  of 
water  from  goiterigenous  springs  and  streams.  Those  authors  who 
believe  in  the  telluric  causation  of  goiter,  attribute  this  acquired  contami- 
nation of  a  stream  to  its  passage  through  certain  geological  formations 
such  as  marine  deposits  of  the  Palaeozoic  age,  or  Triassic  and  Tertian- 
strata,  etc. 

Almost  classical  has  become  the  history  of  the  decline  of  goiter  and 
cretinism  in  Rupperswil  where,  upon  the  advice  of  H.  Bircher,  a  change 
in  the  water  supply  was  made  in  1886,  when  water  from  a  spring  in  the 
goiter-free  Jura  was  conveyed  to  Rupperswil  with  results  as  given  in 
the  following  figures  by  H.  and  E.  Bircher: 


1885 
1886 
1889 

189S 
1907 


59.0  per  cent,  goiterous 
440         " 
25.0 
10. o 


E.  Bircher  considers  his  observations  in  the  village  of  Asp  even  more 
important  than  those  of  the  village  of  Rupperswil.  In  1863  the  statistics 
of  this  village  showed  34  per  cent,  goiter,  8  per  cent,  cretins,  15  per 
cent,  deaf-mutes.  The  drinking  water  was  of  shelly  limestone  deriva- 
tion. In  1907  the  upper  village  introduced  a  new  water  supply,  the 
lower  village,  however,  continued  to  employ  the  old  system.  In  1910 
the  conditions  resulting  from  this  change  were  the  following:  Upper 
village,  6.4  per  cent,  goiter,  8  per  cent,  adults  and  5  per  cent,  school- 
children; lower  village,  38  per  cent,  goiter,  20  per  cent,  adults,  and  66 
per  cent,  school-children.  In  the  lower  village  this  endemic  could  In- 
traced  to  the  individual  houses  which  were  not  connected  with  the  iu w 
water  supply.  As  a  counterpart  to  these  two  examples,  E.  Bircher  cites 
the  community  of  Densburen,  which  in  1908  brought  a  m\\  spring-water 
supply  from  the  shelly  limestone  formation  to  replace  that  from  the 
Jura  used  before.  Within  three  years  after  this  change  was  made 
Bircher  found   a   high    percentage  of  goiter  among  the  school-children. 


246  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

The  exactitude  of  the  results  quoted  above  obtained  by  change  of  drink- 
ing water  in  the  last  three  cases  has  been  recently  contradicted  by  Drs. 
Dieterle,  Hirschfeld  and  Klinger  in  an  article  which  appeared  in  the 
MiLnchener  Med.  Wcchenschrift  for  August  ioth,  191 3,  and  to  which  I 
shall  refer  later  in  connection  with  Bircher's  theory  concerning  the 
influence  of  geological  formation  upon  endemic  goiter. 

That  the  activity  of  the  goiter  causative  factor  is  of  an  evanescent 
and  fleeting  character  has  been  proved  by  numerous  observations.  It 
is  destroyed  bv  ebullition,  and  though  not  destroyed  by  filtration,  it  is 
appreciably  diminished.  Water  which  is  gathered  into  reservoirs  loses 
its  goiterigenous  properties  after  a  certain  period  of  time,  as  does  water 
transported  and  allowed  to  stand  in  bottles  or  casks.  Boussignault  cites 
the  case  of  a  family  living  in  endemic  territory  whose  members  pre- 
served themselves  from  goiter  by  the  simple  precaution  of  letting  the 
drinking  water  stand  two  days  before  using  it.  Often  canalization  or 
piping  of  streams  suffices  to  destroy  their  harmful  power.  The  village 
of  St.  ChafFrev  furnishes  us  with  a  curious  illustration  of  this  condi- 
tion; the  water  from  a  brook  after  being  carried  a  few  hundred  meters 
in  closed  pipes  to  the  village  is  entirely  inoffensive,  whereas,  at  its  source, 
this  same  brook  water  is  intensely  goiterigenous.  It  is  said  that  at  the 
time  of  conscription  the  youths  of  St.  ChafFrev  have  not  omitted  taking 
advantage  of  this  convenient  situation  in  proximity  to  a  goiter  fountain, 
and  have  frequently  traversed  this  short  distance  in  search  of  a  goiter 
exemption  (Berard). 

At  St.  Jean  du  Maurienne  the  endemic  disappeared  within  a  few 
years  after  the  introduction  of  a  new  water  supply  which  was  carried 
in  subterranean  pipes  from  a  spring  at  Jarrier  near  St.  Pancrace,  although 
this  new  water  supply  was  obtained  from  the  midst  of  endemic  territory 
(Repin). 

St.  Lager  observed  that  in  the  village  of  Chateldon  in  Auvergne  the 
canalization  and  collecting  into  a  reservoir  of  torrent  water  was  sufficient 
to  render  the  water  innocuous. 

The  value  of  decantation  in  arresting  the  activity  of  the  goiter 
principle  is  demonstrated  by  an  example  cited  by  Thea  in  1903  in  77 
Policlinic 0.  In  the  town  of  Cuneo  40  per  cent,  of  the  soldiers  in  the 
garrison  became  goiterous  in  the  space  of  5  years;  treatment  remained 
ineffective  in  Cuneo,  but  there  was  an  immediate  amelioration  upon 
change  of  residence.  The  general  population  remained  entirely  unaf- 
fected, although  using  the  same  drinking  water  which  was  collected  in 
vast  reservoirs  and  drawn  ofF  for  distribution  from  the  upper  part  of  the 
last  basin.  Upon  adoption  of  the  same  disposition  for  the  barracks  the 
goiter  epidemic  ceased. 

Goiter  diminishes,  disappears,  or  occurs  in  conformity  with  certain 


THEORIES  REGARDING   THE  ETIOLOGY  OF  GOITER  247 

changes  in  the  drinking  water  whether  naturally  or  artificially  produced. 
The  case  of  Bozel  in  Tarentaise  is  a  typical  example  ot  the  effect  upon 
goiter  of  such  a  change  in  the  water  supply.  In  1848  the  Sardinian 
Commission  counted  900  goiterous  individuals  and  109  cretins  in  a 
population  of  1472  souls,  while  the  inhabitants  of  St.  Bon  at  800  meters 
distance  on  the  opposite  slope  of  the  valley  were  entirely  free  from  such 
infirmities.  Between  the  peasants  living  in  these  two  villages  there 
existed  no  essential  differences  in  houses,  food,  or  habits.  The  degree  of 
material  prosperity  was  the  same.  The  Community  of  Bozel,  realizing 
that  the  only  appreciable  dissimilarity  was  in  the  drinking  water,  brought 
water  to  Bozel  from  a  spring  in  St.  Bon,  and  since  that  time  goiter  and 
cretinism  have  almost  entirely  disappeared.  Berard  reports  in  1907 
that  in  the  neighborhood  of  Bozel  and  Brides  he  observed  only  a  few 
small  goiters. 

The  waters  of  the  Alpine  torrents  have  frequently  been  incriminated 
as  causing  goiter  during  the  summer  months  when  they  are  gray  and 
filled  with  deposits  from  the  glaciers  and  melting  snows.  The  fact  is 
that  during  this  season  the  overland  streams  become  unfit  for  alimen- 
tary purposes,  because  of  the  quantity  of  organic  and  inorganic  matter 
washed  into  them  by  the  heavy  spring  rains  and  the  melting  snow; 
consequently,  in  many  places  where  water  from  non-goitengenous  streams 
is  ordinarily  used  for  drinking  purposes  the  peasant  is  obliged  to  have 
recourse  to  wells,  although  frequently  aware  of  the  danger  he  incurs: 
thence  arises  the  misconception  as  to  the  goitengenous  properties  of  these 
mountain  torrents  at  certain  periods  of  the  year. 

The  endogenous  factors  include  personal  predisposition,  heredity,  sex, 
and  age.  In  goiter  epidemics  it  has  been  constantly  observed  that  when 
a  group  of  people  is  exposed  to  similar  goiterigenous  influences  the 
degree  of  resistance  to  the  disease  varies  with  the  individual,  some  acquir- 
ing goiter  within  a  few  weeks,  others  onlv  after  many  months,  while  a 
certain  proportion  is  altogether  refractor)'  to  the  disease. 

All  of  the  inhabitants  of  endemic  territory  being  equally  exposed  to 
the  endemic  noxa,  it  remains  a  matter  of  conjecture  why  some  of  the 
inhabitants  of  these  countries  remain  refractory  to  the  disease.  Repin 
is  of  the  opinion  that  under  exactly  similar  goitengenous  influences 
individual  temperaments  will  respond  positively  or  negatively  accord- 
ing to  their  preexisting  tendencies  toward  rapidity  or  retardation  in 
the  metabolistic  exchanges. 

I  he  fact  that  the  ingestion  of  goiterigenous  waters  does  not  occasion 
goiter  in  an  individual  case  does  not  authorize  the  conclusion  that  this 
individual  possesses  a  kind  of  immunity  to  the  disease,  but  only  indicates 
that  the  goiter  toxin  is  counteracted  by  the  individual  temperament  in 
question,  the  action  of  the  toxin  being  manifested  m  a  modification  01 


248  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

the  temperament  itself  which  becomes  physiologically  and  psychically  less 
active.  In  short,  the  thyroid  gland  does  not  register  the  results  of  the 
exogenous  factors  only,  but  of  the  exogenous  and  endogenous  factors 
combined. 

Heredity  is  so  much  involved  in  predisposition  and  individual  tem- 
perament that  it  is  difficult  to  assign  to  either  a  separate  and  distinct 
place  among  the  etiological  factors  of  endemic  goiter.  There  seems  to 
be  no  doubt  that  the  endemic  noxa  acting  upon  successive  generations 
of  families  living  in  the  goiter  zone  acquires  an  accumulative  effect. 
For  instance,  many  cases  are  known  of  families  who  have  emigrated 
from  immune  into  endemic  territory  where  the  first  generation  acquired 
goiter,  the  second  showed  symptoms  of  the  cretinoid  degeneration,  and 
the  third  generation  developed  cretinism.  It  is  a  well-established  fact 
that  the  children  of  goiterous  parents  are  more  liable  to  have  goiter 
than  the  children  of  normal  parents,  and  congenital  goiter,  which  is 
not  rare  in  endemic  territory,  may  be  said  never  to  occur  without  goiter 
in  the  mother.  Numerous  cases  have  been  observed  and  reported  of 
mothers  who  have  emigrated  from  endemic  territory,  and  whose  chil- 
dren, born  and  brought  up  far  away  from  the  influence  of  the  endemic 
noxa,  have  nevertheless  developed  goiter.  In  the  case  of  one  family 
that  has  come  under  mv  observation,  the  grandmother,  a  goiter-bearer, 
had  emigrated  from  endemic  territory  in  her  early  youth;  she  settled 
and  married  in  immune  territory  where  her  three  daughters  and  four 
grandchildren  were  all  born  and  all  developed  goiters.  In  the  family 
of  one  daughter  with  two  goiterous  children,  the  husband's  children  by 
a  previous  marriage,  although  living  in  the  same  household,  were  abso- 
lutely normal,  so  there  could  hardly  be  a  question  of  infection  by  contact. 

The  same  has  been  noted,  although  less  frequently,  where  the  father 
is  a  goiter-bearer.  In  one  or  the  other  of  these  categories  may  be  placed 
most  of  the  cases  of  sporadic  goiter  which  are  not  due  to  endemic  influ- 
ences, but  it  must  not  be  forgotten  that  the  endemic  may  be  so  light 
that  only  such  individuals  as  are  highly  predisposed  will  suffer  from  its 
effects  and  this  predisposition  is  itself  a  family  tendency. 

Due  allowance  being  made  for  all  other  determining  conditions, 
there  is  undoubtedly  less  resistance  to  the  goiter  toxin  in  certain  families 
than  others,  just  as  the  tubercular  bacilli  are  able  to  establish  themselves 
with  greater  facility  in  predisposed  families  than  others. 

Billiet,  writing  in  1835,  remarks  that  after  emigration  from  endemic 
territory  the  hereditary  tendency  slowly  disappears,  a  complete  cure 
being  affected  only  in  the  third  generation. 

It  is  difficult  to  determine  to  what  degree  the  hereditary  tendency 
is  an  acquired  characteristic.  Schittenhelm  and  Weichardt  have  col- 
lected family  histories  showing  the  development  of  an  acquired  heredi- 


THEORIES  REGARDIXG  THE  ETIOLOGY  OF  GOITER  249 

tary  tendency  in  families  having  emigrated  from  immune  to  endemic 
territory.  It  is  clearly  established  that  the  dreadful  sequelae  of  endemic 
goiter — deaf-mutism  and  cretinism — are  due  to  the  progressive  and 
cumulative  effect  of  the  endemic  noxa  upon  successive  generations. 
Cretinism  occurs  only  where  endemic  goiter  prevails.  Where  the  endemic 
is  light  only  goiter  is  found,  and  in  proportion  to  the  severity  of  the 
endemic  the  number  of  cretins  and  deaf-mutes  increases.  Statistics 
show  that  80  per  cent,  of  cretins  are  born  of  goiterous  parents. 

Goiter  in  the  mother  is  of  greater  influence  upon  the  children  than 
in  the  father.  It  is,  however,  evident  that  goiter  in  the  parents  cannot 
be  considered  the  cause  of  cretinism,  as  it  is  only  in  endemic  territory 
that  cretinous  children  are  born.  A  goiterous  mother  will  not  bear  a 
cretinous  child  unless  subjected  to  the  endemic  noxa.  Even  cretinous 
mothers  may  bear  intelligent  children  when  removed  from  endemic 
territory.  This  fact  was  understood  by  the  women  of  Sion,  Sierre,  etc., 
in  the  Canton  of  Valais  in  Switzerland,  who  having  given  birth  to  cretin- 
ous children  at  home,  found  that  by  passing  the  period  of  pregnancy 
and  birth  outside  of  endemic  territory,  they  were  able  to  bear  healthy 
children.  Especially  interesting  and  curious  are  the  cases  which  have 
been  observed  from  time  to  time  of  normal  children  born  in  cretinous 
families  where  among  five  or  six  children  bearing  the  stigmata  of 
cretinoid  degeneration,  one  is  born  and  remains  healthy  physically  and 
mentally,  although  subjected  to  the  same  cretinogenous  influences  and 
the  same  daily  contact  as  the  other  members  of  the  family.  This  obser- 
vation has  led  Cerletti  and  Perusini  to  conclude  that  the  cretinogenous 
injun-  must  be  acquired  during  the  intra-uterine  life  and  is  not  transmitted 
at  the  time  of  conception. 

Hydrotelluric  Theory. —  If  we  accept  as  an  established  fact  that  the 
goiter  germ,  whatever  its  nature,  is  most  frequently  conveyed  to  the 
human  body  through  drinking  water,  the  problem  which  at  once  pre- 
sents itself  to  the  investigator  is  to  determine  bv  what  means  the  water 
acquires  the  harmful  properties  in  question.  This  problem  remains 
unsolved  to  this  day  despite  the  most  intensive  scientific  researches. 
Chemical  anal)  sis  has  not  discovered  anything  of  importance  nor  does 
spectroscopic  examination  reveal  unusual  elements  in  goiterigenous 
waters.  Many  theories  that  have  seemed  true  in  one  part  of  the  world 
have  not  been  substantiated  w7hen  applied  to  a  wider  field  of  investiga- 
tion. Grange  attributed  goiter  to  the  presence  of  magnesium  in  the 
water.  St.  Lager,  to  the  presence  of  iron  and  copper  pyrites.  It  is 
undoubtedly  true  that  goiterigenous  waters  are  frequently  heavily 
charged  with  lime,  an  observation  which  was  made  by  McClelland 
and  others  and  lead  to  the  belief  that  hard  water,  or  waters  contain- 
ing lime,  in  large  quantities  are  goiterigenous,  and  that  waters  in  which 


250  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

this  ingredient  is  entirely  absent  do  not  contain  the  goiter  causative 
agent.  On  the  other  hand,  Christener  asserts  that  the  Weissenburg  hot 
lime  waters  are  beneficial  in  the  treatment  of  goiter,  and  Zschokke 
reports  that  the  use  of  Biberstein  water,  of  which  lime  is  a  predomi- 
nating constituent,  causes  goiter  to  disappear. 

Since  no  sufficient  cause  for  the  endemic  could  be  found  in  the 
metallic  and  chemical  constituents  of  the  water,  it  was  thought  that  its 
harmful  effects  might  be  due  to  the  absence  of  some  necessary  element 
such  as  carbon  dioxide,  salt,  absorbed  air,  or  more  especially  10dm. 
Unfortunately  for  the  latter  theory,  analysis  has  proved  that  goiter- 
igenous  and  even  non-goiterigenous  waters  frequently  contain  the  same 
quantity  of  iodin,  and  instances  are  known  where  water  particularly  rich 
in  iodin  causes  goiter,  as  in  the  case  cited  by  Chatin  at  Beaulieu  in  the 
Department  of  Oise.  On  the  other  hand,  it  must  not  be  forgotten  that 
excellent  results  in  the  treatment  of  goiter  have  been  obtained  by  the 
exclusive  use  of  distilled  drinking  water. 

Many  investigators  are  convinced  of  the  parasitic  origin  of  goiter. 
According  to  our  actual  knowledge  of  the  disease  and  its  cause,  it  seems 
probable  that  in  this  direction  must  lie  the  ultimate  solution  of  the 
problem,  but  until  now,  in  spite  of  the  highly  perfected  means  of  inves- 
tigation possessed  bv  modern  science,  it  has  been  impossible  to  isolate 
the  microbe.  Constant  experiments  by  many  investigators  with  the 
bacteria  contained  in  goiters  have  led  to  no  positive  results.  Ewald 
says,  "  If  water  be  of  influence  in  the  origin  of  goiter — and  this  does 
not  admit  of  doubt — the  cause  can  only  lie  in  a  contagium  vivum, 
or  organic  poison."  Schittenhelm  and  Weichardt  find  that  the  general 
mass  of  evidence  indicates  a  parasitic  infection  of  the  water.  This  is 
also  the  opinion  of  McCarrison   and  many  others. 

From  the  earliest  days  of  scientific  research  as  to  the  etiology  of 
endemic  goiter  to  our  own  times,  many  investigators  have  sought  to  estab- 
lish a  correlation  between  certain  geological  formations  and  endemic 
goiter.  The  fact  that  the  quality  of  the  drinking  water  must  be  influ- 
enced by  the  character  of  the  soil  from  which  it  springs  has  led  to  the 
association  of  these  two  elements. 

Virchow,  in  summing  up  the  results  of  his  researches  concerning 
cretinism  in  Lower  Franconia  writes,  "I  hold  the  nature  of  the  water  to 
be  the  essential  factor,  but  believe  this  to  be  determined  by  the  geologi- 
cal formation  of  the  soil  from  which  it  springs."  Kocher  considers 
drinking  water  as  "the  only  paramount  factor  through  which  the  soil 
could  exercise  such  a  determining  influence  upon  the  health  of  the 
inhabitants  as  in  the  causation  of  endemic  goiter."  Cardinal  Billiet, 
whose  investigations  were  made  in  Savoy,  was  among  the  first  to  fol- 
low this  line  of  research,  and  as  early  as   1835  maintained  that  goiter 


THEORIES  REGARDIXG   THE  ETIOLOGY  OF  GOITER  2.51 

was  endemic  on  the  argillaceous,  calcareous  and  micaceous  schists,  and 
absent  on  the  Jurassic  and  cretaceous  formations.  McClelland  at  about 
the  same  period  made  investigations  in  Kumaun  in  the  Himalayas  where 
his  observations  led  him  to  conclude  that  the  argillaceous  schists,  sili- 
ceous sandstones,  amphibolites,  granite,  and  the  micaceous  slates  were 
free  from  goiter  which  prevailed  with  intensity  on  limestone  formations. 
McClelland  further  writes,  "The  exciting  cause  has  been  traced  to  cer- 
tain strata  of  the  earth  under  circumstances  calculated  pointedly  to 
suggest  that  water  is  the  medium  by  which  it  is  conveyed  to  the  bodies 
of  men." 

Grange,  who  studied  the  question  in  the  Alps,  considers  excess  of 
magnesia  in  the  water  to  be  the  cause  of  goiter.  He  finds  that  while 
goiter  exists  on  the  marine  Molasse,  it  is  most  prevalent  on  the  Triassic 
formations,  i.  e.,  the  shelly  limestones,  marl,  and  especially  the  mag- 
nesian  limestones  of  the  Dolomitic  formations.  He  found  the  coal 
measures  and  granite  formations  free.  These  conclusions  of  Grange 
have  been  corroborated  in  Germany  by  Virchow,  who  finds  the  shelly 
limestone  (muschelkalk)  of  Lower  Franconia  intensely  infected,  and  a 
decided  retrogression  of  the  disease  upon  the  Keuper  and  sandstone, 
and  bv  Meyer,  Diedel,  and  Heidenreich,  in  Middle  Franconia.  In 
France  Garrigou  finds  the  disease  associated  with  the  marl  and  Dolo- 
mitic clavs  of  the  Pyrenees  and  New  Granada.  Boussignault  reports 
the  endemic  prevalent  on  the  limestone  rocks.  In  1843  Escherich  found 
goiter  prevalent  in  Lower  Swabia  on  the  Keuper  and  shelly  limestone 
(muschelkalk)  and  absent  on  the  Jurassic  formations  of  Upper  Swabia, 
and  the  chalk  formations  in  England  and  France. 

De  Beaumont  has  demonstrated  in  Savoy  that  Jura,  granite  and 
chalk  are  free  from  goiter,  while  on  the  Eocene  and  Triassic  formations 
the  endemic  is  intense.  St.  Lager,  to  whom  we  are  indebted  for  impor- 
tant investigations  as  to  the  causes  of  goiter  and  cretinism,  has  made  a 
most  careful  study  of  the  geological  conditions  existing  in  goiterigenous 
regions  and  has  concluded  that  while  ordinarily  granite,  gneiss,  mica 
schists,  and  the  quartziferous  porphyries  are  free  from  the  endemic, 
this  is  not  true  when  they  are  covered  with  a  superficial  stratum  of 
metalliferous  rocks.  Although  rare  on  volcanic  soil,  goiter  is  found 
near  the  Solfatara  where  the  sulphurous  emanations  attack  the  ferru- 
ginous claws.  The  endemic  is  to  be  found  on  the  magnesium  limestones 
of  the  Lias,  on  the  red  clays,  on  the  dolomite  and  gypsum  of  the  1  rias, 
and  on  the  Molasse.  On  alluvium  or  diluvium  the  disease  does  not  exist 
unless  tins  soil  has  been  transported  from  goiterigenous  regions. 

According  to  St.  Lager,  the  endemic  coincides  with  the  existence  of 
metalliferous  and  siliceous  rocks,  the  influence'  of  iron  pyrites  being 
particularly  injurious.     Baillarger  finds  goiter  widely  disseminated  on 


252  ETIOLOGY  OF  ENDEMIC  GOITER  AXD  CRETINISM 

Dolomitic  rocks  in  France.  Hirsch,  in  his  general  summing  up  of  the 
situation  in  i860,  concludes  that  although  no  geological  formation  pre- 
cludes the  possibility  of  occurrence  of  goiter  or  cretinism,  both  diseases 
are  far  more  prevalent  on  the  older  formations,  including  the  Trias 
group,  than  on  newer  strata.  Thus  the  general  consensus  of  opinion 
among  investigators  seems  to  indicate  a  probable  relation  between  the 
character  of  the  soil  and  endemic  goiter,  the  injurious  influence  upon 
the  human  organism  being  attributed  to  the  mineralogical  or  geological 
structure  of  the  soil. 

The  hydrotelluric  theory  of  the  etiology  of  goiter  received  its  most 
important  contribution  in  1883  from  H.  Bircher  in  his  valuable  and 
interesting  monograph  on  Endemic  Goiter.  Bircher  observed  that  the 
endemic  prevailed  with  intensity  among  the  villages  situated  on  the 
right  bank  of  the  River  Aare  where  the  soil  formation  was  marine 
Molasse,  while  among  the  inhabitants  of  the  villages  situated  upon  the 
Jura  formation  of  the  left  bank  goiter  was  absent  with  the  single  exception 
of  one  village  which  stood  upon  a  strip  of  muschelkalk  (shelly  limestone) 
extending  into  the  midst  of  the  Jurassic  formation.  Bircher  based  these 
observations  upon  personal  examination  of  the  school-children  in  this, 
his  home  district.  He  next  proceeded  to  consult  the  military  statistics, 
with  the  result  that  his  previous  findings  were  verified,  not  only  for  the 
Canton  of  Aarau,  but  also  for  the  whole  of  Switzerland.  Upon  further 
extended  and  painstaking  researches  he  became  convinced  that  in 
Switzerland,  which  is  of  all  European  countries  the  most  severely 
afflicted  with  goiter,  the  disease  only  occurs  upon  the  sediments  of  Trias- 
sic,  Eocene,  and  Miocene  seas,  and  that  the  Jura  and  chalk  as  well  as 
the  fresh-water  deposits  are  free  from  goiter.  Furthermore,  after  study- 
ing the  geological  conditions  in  relation  to  endemic  goiter  in  other  coun- 
tries, Bircher  concludes  as  follows: 

1.  Goiter  only  occurs  upon  marine  deposits  and  especially  upon 
marine  sediments  of  the  Paleozoic,  Triassic,  and  Tertiary  periods. 

2.  That  the  eruptive  rocks,  the  crystalline  rocks  of  the  Archaean 
groups,  the  sediments  of  the  Jurassic,  Cretaceous,  and  Quaternary  seas 
and  all  fresh-water  deposits  are  free  from  goiter. 

When  the  disease  is  found  on  geological  formations  of  the  second 
class,  this  is  due  either  to  the  fact  that  this  formation  consists  of  a  com- 
paratively thin  layer  covering  a  substratum  of  rocks  of  the  first  class, 
so  that  the  sources  of  springs  and  wells  are  not  derived  from  the  super- 
ficial upper  stratum,  but  extend  into  the  underlying  rockbed,  or,  to  the 
fact  that  these  goiter  foci  may  be  located  on  isolated  islands  of  rock  of 
the  first  class  which,  when  covering  any  considerable  area  of  the  earth's 
surface,  form  the  garden  soil  of  endemic  goiter.  On  the  other  hand,  the 
injurious  influence  of  such  formations  may  be  lessened  or  may  entirely 


THEORIES  REGARDIXG  THE  ETIOLOGY  OF  GOITER  253 

disappear  bv  superimposed  fresh-water  deposits,  the  endemic  occur- 
ring only  where  the  underlying  marine  strata  breaks  through  the  fresh- 
water sediment.  Bircher  explains  the  greater  frequency  and  intensity 
of  the  endemic  in  mountainous  regions  by  the  fact  that  in  bursting 
through  the  earth's  crust,  the  older  strata  of  the  Paleozoic  and  Meso- 
zoic  periods  have  been  pushed  to  the  surface  as  is  especially  the  case  in 
the  Alps.  In  other  parts  these  strata  have  been  so  elevated  that  the 
later  seas  never  covered  them  as  with  the  Trias  on  both  sides  of  the 
Rhine.  This  is  also  the  explanation  of  the  prevailing  endemic  in  central 
Switzerland  and  Styna  where  the  Miocene  marine  deposits  form  the 
upper  stratum  of  the  earth's  crust  because  of  the  continental  elevation 
which  prevented  the  superimposition  of  later  sediments. 

Low-lying  river  valleys  are  also  frequently  goiter  centers  because 
the  stream  cuts  through  the  earth's  crust  and  uncovers  the  underlying 
formations  bringing  them  to  the  surface  where  they  necessarily  produce 
their  pernicious  effect  upon  the  drinking  water. 

In  support  of  these  conclusions  of  H.  Bircher  his  son,  E.  Bircher, 
has  contributed  a  very  valuable  and  convincing  mass  of  evidence 
obtained  from  investigations  and  experiments  which  have  been  executed 
with  the  utmost  care  and  attention  to  detail.  One  of  these  experiments  is 
particularly  interesting  as  having  a  special  bearing  upon  the  matter 
under  consideration. 

In  an  early  publication  Bircher  recorded  an  unsuccessful  attempt 
to  artificially  create  goiterigenous  water  by  placing  sterile  water  in 
direct  contact  with  rock  of  one  of  the  formations  upon  which  Bircher 
affirms  that  goiter  occurs.  The  failure  of  the  first  experiment  he 
attributed  to  defective  preparations,  probably  due  to  the  fact  that  the 
rock  used  was  taken  from  the  mouth  of  the  Rupperswil  spring,  while 
the  infection  of  the  water  was  doubtlessly  drawn  from  the  substratum 
with  the  source  of  the  spring  itself. 

For  his  later  experiment  he  used  stone  from  the  middle  marine 
Molasse.  After  placing  a  cubic  meter  of  this  rock  in  a  wooden  recep- 
tacle, he  filled  the  receptacle  to  the  brim  with  distilled  water  and  allowed 
the  water  at  first  to  remain  in  contact  with  the  stone  from  10  to  14 
days,  but  later  only  3  days.  This  water  was  given  to  rats  to  drink. 
After  a  period  of  about  nine  months,  the  rats  subjected  to  this  experiment 
developed  hyperplasia  of  the  thyroid  gland. 

Bircher  considers  that  the  results  obtained  from  this  experiment 
clearly  establish  the  connection  of  the  goiter  toxin  with  the  soil,  and  its 
limitation  to  certain  geological  formations.  As  to  the  actual  primary 
cause  of  this  infection,   Bircher  acknowledges   that  it  is  still   unknown. 

It  is  at  present  impossible  to  determine  whether  the  toxin,  whatever 
its  nature,  is  due  to  purely  chemical  processes  within  the  rock  itself,  or 


254  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

whether  the  active  generating  principle  of  the  toxin  must  be  sought  in 
a  living  organism  which  finds  its  culture  media  on  the  geological  forma- 
tions incriminated.  Personally,  Bircher  is  convinced  that  the  goiter 
toxin  is  of  colloidal  nature  and  that  it  is  washed  or  soaked  out  of  the 
rocks  by  water.  He  also  made  a  number  of  interesting  experiments 
upon  rats  in  order  to  prove  that  the  goiter-causing  substance  must  be  in  a 
colloidal  state.  In  these  experiments,  he  finds  that  these  toxic  substances 
are  not  removed  from  water  by  filtration  through  a  Berkefeld  filter, 
but  that  dialysis  removes  the  goiter-producing  substance  from  water, 
and  that  the  substances  separated  from  the  water  and  remaining  on  the 
membrane  of  the  dialyzer  are  likewise  capable  of  producing  goiter. 

Animals  experimented  upon,  acquired  goiter  when  drinking  water 
from  goiter  springs  both  in  the  natural  state  and  after  having  passed 
through  the  Berkefeld  filter.  No  thyroid  enlargement  occurred  when 
rats  were  given  water  that  had  passed  through  the  dialyzer,  but  when 
the  substances  separated  from  the  water  by  the  membrane  were  fed 
to  them,  they  rapidly  acquired  goiter,  the  degenerative  changes  in  the 
cells  of  the  thyroid  gland  being  peculiarly  severe.  As  the  goiter  toxin 
cannot  go  through  the  membrane  of  the  dialyzer,  it  must,  according  to 
Bircher,  be  of  colloidal  nature.  Moreover,  through  centrifugation  water 
from  goiter-producing  springs  may  be  rendered  innocuous,  and  as  it  is 
an  established  fact  that  colloid  substances  may  be  coagulated  when 
centrifugated,  this  is  particularly  significant.  Many  investigators  have 
found  that  even  severe  shaking  of  the  vessel  containing  goiter-producing 
water  is  sufficient  to  render  it  innocuous.  Bircher  finds  that  the  general 
indications  of  these  observations  are  decidedly  against  the  probability 
that  goiter  is  caused  in  a  direct  manner  by  a  microorganism,  as  nothing 
in  bacteriology  has  heretofore  shown  that  water  containing  bacteria 
could  be  rendered  harmless  by  standing,  shaking,  or  by  centrifugation. 

In  more  recent  experiments  Bircher  found  that  goiter-producing 
water  may  become  free  from  toxin  by  filtration  through  a  layer  of  pow- 
dered charcoal  30  centimeters  thick.  The  success  of  this  experiment, 
Bircher  thinks,  can  only  be  explained  by  the  colloidal  nature  of  the 
toxin  which  admits  of  a  process  of  absorption  and  is  held  fast  in  the 
powdered  coal  as  the  water  passes  through.  The  addition  of  various 
chemical  substances  to  the  water  proved  destructive  to  the  goiter  toxin. 
Zinc  hydroxide  Zn(OH.)2  is  known  to  possess  the  property  of  separating 
colloidal  substances  in  solution  and  the  addition  of  1  to  10  g.  Zn(OH)2 
to  1  liter  of  goiter  water  proved  sufficient  to  render  the  water  innocuous. 
The  quantity  of  Zn(OH)2  used  was  so  small  that  it  could  scarcely  have 
been  bactericidal  in  its  effect.  H202  even  when  used  in  exceedingly  small 
quantities  produced  the  same  results.  Finally,  boiling  renders  goiter- 
lgenous  waters  harmless. 


THEORIES  REGARDING   THE  ETIOLOGY  OF  GOITER  255 

Bircher  was  able  to  demonstrate  by  the  use  of  the  stalagmometer 
that  the  superficial  tension  differs  in  goiterigenous  and  non-goiter- 
igenous  waters.  The  stalagmometer  shows  a  considerable  increase  in 
the  number  of  drops  obtained  from  the  goiterigenous  water  over  the 
non-goiterigenous.  Of  the  57  waters  examined,  the  21  which  were 
goiter-free  showed  about  56.45  drops,  never  exceeding  57.8,  whereas 
the  remaining  36  goiter  waters  showed  an  average  of  60  drops,  sometimes 
more,  but  never  less  than  59  drops.  The  capillary  attraction  would 
therefore  seem  to  be  lower  in  goiterigenous  waters,  and  consequently 
its  superficial  tension  would  be  lower. 

Bircher  next  proceeded  to  make  an  ultramicroscopic  examination  of 
goiter  water.  At  the  time  of  his  report  he  had  examined  eight  springs 
in  Aarau  and  vicinity.  These  goiter  waters  constantly  showed  a  sur- 
prisingly large  number  of  ultramicroscopic  particles,  or  molecular  con- 
stituents. These  particles  all  presented  the  same  appearance.  They 
were  round  or  slightly  oval  in  shape,  and  showed  the  same  continuous 
movements  in  all  directions  that  are  usually  to  be  seen  in  substances  in 
a  colloidal  state,  when  under  ultramicroscopic  examination,  as  for 
instance,  colloidal  Argentum  nitric,  or  colloidal  Zn(OH)2.  Whether 
these  particles  are  of  chemical  or  bacterial  origin   remains  hypothetical.1 

In  summing  up  the  conclusions  of  both  H.  and  E.  Bircher,  Ewald 
remarks  that,  while  the  indications  are  that  goiter  occurs  only  in  dis- 
tricts of  certain  geological  formations,  it  is  not  always  present  where 
these  formations  exist.  In  fact  there  must  exist  a  specific  infection  or 
pollution  of  these  rocks  for  them  to  produce  goiterigenous  waters, 
and  to  such  infection  onlv  the  formations  in  question  are  liable,  exactly 
as,  for  example,  certain  mushrooms  can  only  grow  upon  soil  of  a  certain 
character. 

Johannesen  corroborated  these  findings  in  Norway.  His  researches 
being  carried  out  in  a  district  where  the  geological  conditions  arc-  simple 
and  well  known.  Me  finds  no  goiter  on  the  primitive  rocks  where  they 
are  free  from  an  admixture  of  Mesozoic  or  Tertiary  sediment.  Of  the 
goiter-bearers  96.6  per  cent,  are  to  be  found  on  the  Silurian  or  Devonian 
formations.  He  cites  one  instance  of  a  farm  where  goiter  occurred,  and 
which,  according  to  the  geological  map,  was  situated  upon  primitive 
rock.  Investigation,  however,  proved  the  map  to  be  in  error,  and  that 
the  farm  was  lying  upon  the  extreme  limit  of  the  Silurian  argillate. 

Holler,  in  his  researches  concerning  cretinism  in  the  district  of  I  olz 
in  Bavaria,  reports  the  endemic  intense  111  sections  of  the  Miocene  and 
Eocene  formations,  especially  severe  upon  the  Eocene  flysch  and  upper 

1  l);is  Kropf  Problem  von  Dr.  Eugen  Bircher.  Festschrift  lltrr  Dr.  Heinrich 
Bircher. 


256  ETIOLOGY  OF  ENDEMIC  GOITER  AXD  CRETIMSM 

shell  limestone,  and  almost  completely  subsiding  where  the  fresh-water 
Molasse  and  red  sandstone  predominate. 

James  Berry  found  that  in  England  the  endemic  coincided  with 
calcareous  formations,  prevailing  not  only  on  limestone,  but  also  on 
calcareous  sandstones  (McCarnson). 

Kocher  does  not  altogether  agree  with  the  findings  of  Bircher.  His 
own  researches  in  the  Canton  of  Berne  lead  him  to  believe  that  goiter 
is  not  limited  to  the  regions  of  the  geological  formations  indicated  by 
Bircher.  With  the  assistance  of  25  of  his  pupils  he  examined  76,606 
school-children  between  the  ages  of  7  and  15  years,  and  found  that  in 
some  parts  of  the  Bernese  Oberland  from  80  to  90  per  cent,  of  the 
children  suffered  from  the  endemic.  While  the  disease  was  far  less 
frequent  upon  the  Jurassic  formations  than  upon  the  marine  Molasse, 
he  found  that  the  former  was,  nevertheless,  not  exempt,  and  that  even 
the  upper  and  lower  fresh-water  Molasse  were  not  immune.  Kocher 
finds  the  endemic  intense  upon  the  Jurassic  formations  of  the  Bernese 
Oberland.  He  is  inclined  to  attribute  these  deviations  in  the  behavior 
of  the  endemic  in  sections  situated  upon  similar  rock  formations,  though 
in  different  parts  of  Switzerland,  to  the  presence  and  admixture  of 
impurities  in  the  soil,  and  above  all,  to  organic  matter. 

Kocher  concluded  that  the  determining  factor  does  not  he  in  the 
mineralogical  or  chemical  constitution  of  the  soil,  but  in  its  greater  or 
lesser  pollution,  and  in  consequence  that  the  culture  media  for  the 
microorganism  or  toxins  involved  may  extend  far  beyond  the  limits 
indicated  by  Bircher  (Ewald). 

Investigations  made  by  the  late  Dr.  Ernest  Pagenstecher  in  the 
middle  Rhine  district  and  in  Nassau  support  in  general  the  Bircher 
theory.  He  found  the  endemic  most  pronounced  upon  Devonian  slate. 
Where  this  formation  has  been  covered  with  a  fresh-water  formation, 
the  endemic  disappears.  Pagenstecher  does  not  find  the  goiter  espe- 
cially pronounced  among  children  in  the  sense  of  Schittenhelm  and 
Weichardt. 

In  Hesse's  researches  concerning  the  distribution  of  endemic  goiter 
in  the  Kingdom  of  Saxony,  he  was  unable  to  corroborate  entirely 
Bircher's  theory  as  to  the  regular  coincidence  of  certain  geological  forma- 
tions and  goiter.  In  Saxony,  as  elsewhere,  the  seventy  of  the  endemic 
increases  within  the  high-lying  mountainous  districts,  but  in  contra- 
distinction to  Bircher,  Hesse  found  the  greatest  number  of  goiters  upon 
the  eruptive  Muscovite  gneiss  and  Ebenstock  granite,  while  the  Devonian, 
Silurian,  and  carboniferous  formations  of  the  Paleozoic  periods  were 
relatively  free.  In  agreement  with  Bircher,  Hesse  found  that  the 
endemic  was  particularly  intense  upon  the  earliest  strata  of  the  marine 
sediment  of  the  older  Paleozoic  period,  especially  the  lower  Cambrian. 


THEORIES  REGARDING  THE  ETIOLOGY  OF  GOITER  257 

Recent  investigations  were  made  by  Lobenhoffer  in  Lower  Fran- 
conia  which  entirely  agree  with  the  laws  established  by  Bircher.  Appar- 
ent deviations  from  these  results  were  almost  invariably  found  to  be 
based  upon  errors  in  the  geological  map.  These  contra-indications  were 
corrected  upon  comparing  the  Lepsius  map,  which  proved  inexact  in 
some  places,  with  the  more  detailed  Munich  map.  Lobenhoffer  affirms 
that  the  intrusion  of  small  wedges  of  shell}-  limestone  amidst  other 
formations  will  invariably  augment  the  intensity  of  the  goiter  endemic. 
He  believes  these  laws  to  be  so  exact  that  goiter  may  be  considered  a 
veritable  Leit-fossil  by  the  aid  of  which  one  can  trace  stratigraphical 
conditions  despite  errors  of  classification  in  existing  geological  maps. 
Where  an  apparent  exception  occurs,  closer  examination  will  prove 
either  that  a  mistake  has  been  made  in  classing  the  formation  in  ques- 
tion, or  that  the  outcropping  stratum  is  of  so  little  density  that  the  springs 
and  wells  penetrate  into  an  underlying  bed  of  Tertian",  Triassic,  or 
Paleozoic  marine  sediment.  These  views  are  shared  by  Breitner, 
Wegelin,  etc. 

Schittenhelm  and  Weichardt  recently  made  investigations  in  the 
Kingdom  of  Bavaria  where  their  findings  did  not,  on  the  whole,  agree 
with  Bircher's  theory.  They  report  the  endemic  prevalent  upon  the 
Archaean  rocks  of  the  Bavarian  Forest,  and  upon  Keuper,  fresh-water 
Molasse,  and  Diluvium,  all  of  which,  according  to  Bircher's  theory, 
should  be  immune. 

Schittenhelm  and  Weichardt  are  convinced  by  their  investigations 
in  Bavaria  that  water  issuing  from  one  and  the  same  rock  formations 
may  produce  goiter  in  one  locality  and  be  harmless  in  another,  tin- 
all  v,  thev  conclude  that,  "The  primary  determining  factor  for  the 
endemic  distribution  of  goiter  does  not  lie  in  the  geological  formation, 
but  in  the  infection  of  the  water  itself  which  may  indeed  be  influenced 
by  certain  rock  and  soil  conditions  but  not  according  to  fixed  laws." 
They  further  consider  that  the  element  most  conducive  to  endemic  goi- 
ter is  the  mountainous  character  of  the  country.  It  is  interesting  to 
compare  this  summary  with  the  conditions  which  McCarrison  groups 
together  as  ideal  for  the  development  of  goiter,  "An  agricultural  popu- 
lation living  on  a  porous  soil,  which  soil  contains  much  organic  matter, 
and,  because  of  its  porosity  or  slope,  admits  of  the  ready  passage-  of 
organic  matter  into  the  unprotected  streams  and  wells  that  are  the  water 
supplv  of  the  people.  It  is  in  the  mountainous  countries  where  lime- 
stone rocks  abound  that  these  conditions  are  most  frequently  found  m 
combination." 

Schittenhelm  and  Weichardt  further  remark  that  the  occurrence  of 
endemic  goiter  in  sections  upon  underlying  Archaean  rocks  in  bur  out 
region  of  the  earth's  surface  would  be  sufficient  to  invalidate  the  Bircher- 

17 


258  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

toxin  theory,  as  it  is  impossible  for  an  organic  colloidal  toxin  to  be 
washed  out  of  Archaean  rocks  which  are  absolutely  free  from  organic 
matter,  or  from  eruptive  rocks  which  reached  the  earth's  surface  with 
many  thousand  degrees  of  heat  in  a  molten,  liquid  state.  The  most 
interesting  observation  made  by  these  authors  is  related  to  the  incidence 
of  goiter  among  children  which  they  claim  reaches  its  maximum  at 
about  the  tenth  year  and  decreases  after  that  age.  The  frequency  of 
goiter  among  children  is  so  great  that  it  suggests  an  analogy  with  the 
findings  of  Koch  in  his  investigations  of  malaria,  a  disease  which  attacked 
all  children  in  endemic  territory  during  early  life,  and  was  followed  by 
the  development  of  a  natural  immunity  in  the  course  of  time.  Schitten- 
helm  and  Weichardt  suggest  that  in  the  regions  where  the  goiter  endemic 
is  intense  the  entire  population  may  be  affected  during  early  childhood 
in  greater  or  less  degree,  the  majority  acquiring  a  sort  of  immunity 
later  on.  These  observations  are  particularly  significant  when  we  remem- 
ber Kocher's  findings  of  from  80  to  90  per  cent,  thyroid  hyperplasia 
among  the  school-children  of  some  parts  of  the  Canton  of  Berne.  It  is, 
moreover,  an  established  fact  that  the  young  are  peculiarly  liable  to 
develop  goiter  when  transferred  from  goiter-free  to  endemic  territory,  as 
has  been  proved  by  the  many  epidemics  in  boarding  schools,  seminaries, 
and  barracks  cited  in  our  chapter  on  Epidemic  Goiter. 

While  it  may  be  considered  as  an  established  fact  that  the  goiter 
toxin  may  be  transmitted  to  the  human  body  through  drinking  water 
(although  even  this  is  denied  by  some  investigators,  Kutschera,  Taus- 
sig, etc.),  few  of  the  scientists  of  today  still  believe  that  the  cause  of 
goiter  lies  within  the  geological  formation  itself.  We  agree  with  Schitten- 
helm  and  Weichardt  that,  "It  is  incredible  that  such  virulent  activity 
should  be  attached  to  a  toxin  derived  from  organic  matter  which  has  been 
buried  within  the  earth  for  many  hundred  thousand  years."  More  prob- 
ably, when  the  solution  is  obtained,  the  cause  will  be  found  to  lie  within 
conditions  which  are  quite  subject  to  our  control,  as  has  been  the  case 
for  so  many  devastating  epidemic  diseases  such  as  malaria,  yellow  fever, 
and  so  forth.  A  curious  fact  is  that  in  those  countries  where  the  endemic 
is  light,  although  clearly  defined,  goiter  wells  are  unknown,  but  as  one 
advances  into  the  districts  of  high  endemicity,  the  noxious  qualities  of 
the  waters  concentrate  and  intensify  until  one  comes  to  the  well-known 
goiter  fountains  whose  waters  were  dreaded  even  by  the  ancients  and 
which  have  kept  their  evil  fame  unto  this  day. 

It  has  been  well  said  that  the  Panama  Canal  was  built,  not  by 
engineers,  but  by  doctors,  so  why  should  their  high  courage,  insight  and 
perseverance  fail  before  this  oldest  and  most  baffling  of  the  endemic 
maladies?  Through  the  process  of  elimination  the  circle  of  probabili- 
ties   and    possibilities    must   become    smaller   and    concentration    conse- 


THEORIES  REGARDING  THE  ETIOLOGY  OF  GOITER  259 

quently  higher  in  the  remaining  fields  of  investigation.  The  solution 
will  doubtless  come  in  this,  as  it  has  in  other  problems,  when  least 
expected. 

Repin's  or  Plutonian  Theory. — Dr.  Repin,  of  the  Pasteur  Institute, 
has  published  several  interesting  articles  upon  the  "Nature  and  Origin 
of  Goiterigenous  Waters,"  which  he  associates  with  mineral  springs. 
As  a  general  proposition  he  affirms  that  endemic  goiter  is  never  absent 
in  a  mountain  range  of  any  importance,  and  that  in  proportion  to  the 
height  and  precipitousness  (i.  <?.,  geologically  recent)  the  endemic  is 
more  intense.  The  disease  attains  its  maximum  upon  the  mountain 
slopes  and  adjacent  valleys  and  plains,  the  upper  zone  being  compara- 
tively free. 

In  order  to  make  his  theory  clear,  Repin  gives  a  brief  summary  of  the 
history  of  the  origin  of  mountain  chains.  Mountain  chains  occur  along 
lines  of  weakness  in  the  earth's  crust  where  there  has  been  a  subsidence 
or  depression  between  two  more  rigid  masses  of  the  lithosphere. 
These  lines  of  subsidence  are  called  geosynclinals,  and  when  through 
contraction  of  the  earth's  surface  they  are  subjected  to  lateral  or  tan- 
gential thrusts  from  the  harder  formations  between  which  they  lie,  the 
space  above  them  alone  being  free,  these  vast  masses  are  folded,  pushed 
upward,  and  forced  one  over  the  other  in  stratigraphical  disorder.  When 
this  upheaval  is  terminated,  those  parts  of  the  newly  formed  chain 
which  are  not  on  a  firm  basis  subside  and  sink,  the  solid  central  mass 
usually  maintaining  its  equilibrium  while  the  slopes  and  base  of  the 
synclinal  fold  are  rent  with  innumerable  fractures  and  dislocations  or 
faults. 

The  dimension  of  these  fractures  and  the  mechanism  of  their  produc- 
tion indicate  that  the  entire  density  of  the  lithosphere  must  be  concerned. 
1  hey  therefore  open  a  door  of  communication  between  the  atmosphere 
and  the  igneous  interior  of  the  earth.  The  earliest  of  these  fractures 
have  been  filled  with  incandescent  matter  which  in  the  process  of  solidi- 
fication has  formed  the  veins  of  quartz,  granite,  porphyry,  which  we 
often  find  penetrating  stratified  deposits.  Later  these  interstices  formed 
chimneys  where  highly  mineralized  vapors  condensed  when  reaching 
the  cooler  regions  near  the  earth's  surface  and  gave  rise  to  the  metal- 
liferous veins  so  abundant  in  secondary  and  tertian-  formations.  At  the 
present  time  only  the  most  recent  fractures  remain  open  and  the  visible 
signs  of  the  inner  eruptive  energy  are  limited  to  geysers,  mineral  springs, 
and  exhalations  of  combustible  gas  and  carbon  dioxide.  Repin  affirms 
that  true  mineral  springs  are  precisely  of  this  class  and  arise  from  great 
depths  in  the  earth's  interior  through  the  aforesaid  fractures  of  the 
lithosphere.  They  an-  known  ;is  hypogene,  native^  or  plutonic  waters. 
1  heir  most  important  attribute  is  the  powerful  action  which  they  exer- 


260  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

cise  upon  the  general  metabolism  and  which  is  possessed  by  no  other 
medical  agent.  Analysis  of  the  composition  of  these  waters  does  not 
account  for  their  peculiar  and  well-established  property,  which  is  tran- 
sient and  fleeting  in  character,  these  waters  losing  much  of  their  action 
after  transportation,  the  best  therapeutic  results  from  their  use  being 
obtainable  only  at  the  source  of  the  springs  themselves. 

Since  the  discovery  of  radio-activity  it  was  natural  for  investigators 
to  turn  in  that  direcmn,  and  it  was  found  that  the  majority  of  mineral 
springs  were  highly  radio-active.  Repin  believes  a  high  radio-active 
count  to  be  a  necessary  condition  of  plutonic  waters.  In  the  great 
melting  pot  at  the  earth's  center  the  water  issuing  from  the  liquefying 
rocks  must  absorb  radium  emanations  in  abundance  and  carry  them  to 
the  earth's  surface  as  it  rushes  upward  through  the  lines  of  fracture 
already  described. 

Upon  the  foregoing  basis  Repin  assumes  the  three  necessary  charac- 
teristics of  mineral  waters  to  be: 

i.  A  general  physiological  action  sui  generis,  which  he  describes  as 
affecting  the  general  metabolism. 

2.  They  must  emerge  along  the  lines  of  fractures  in  the  earth's 
crust. 

3.  Their  radio-active  count  must  be  high,  this  being  (he  considers) 
the  necessary  property  of  hvpogene  waters. 

Repin  believes  these  three  attributes  to  be  common  to  mineral  and 
goiterigenous  waters  and  that  it  is  therefore  legitimate  to  conclude  that 
they  belong  to  the  same  family,  i.  e.,  that  they  are  hvpogene,  native,  or 
eruptive  waters.  Examinations  of  goiterigenous  waters  from  St.  Jean- 
du-Maurienne  and  other  goiter  wells  in  the  Maurienne,  Oisans,  and 
Briconnais  showed  them  to  be  radio-active  in  the  same  degree  as  the 
mineral  springs  of  Dax  and  Contrexeville. 

These  native  waters  have  been  in  contact  with  the  igneous  interior 
of  the  earth  where  aqueous  vapors,  mineral  fumaroles,  radio-active 
derivations  and  rare  gases  take  part  in  a  cycle  of  reactions  from  which 
result,  under  the  appearance  of  a  simple  aqueous  solution,  a  complex 
composition  which  we  have  not  yet  been  able  to  analyze.  This  might 
be  called  the  plutonian  theory.  Here  Repin  recalls  St.  Lager's  theory  as 
to  the  etiological  influence  of  metalliferous  veins,  especially  iron  pyrites, 
which  he  invariably  found  associated  with  goiterigenous  springs,  this 
erroneous  conclusion  being  due  to  the  fact  that  metalliferous  veins  and 
goiterigenous  springs  occur  along  the  same  lines  of  dislocation  in  the 
earth's  crust. 

To  what  element  must  be  assigned  the  principal  role  in  the  complex 
aggregate  which  constitutes  a  true  mineral  water?  Do  the  mineral 
constituents   preserve   a    temporary    instability   which    might    facilitate 


THEORIES  REGARDING  THE  ETIOLOGY  OF  GOITER  261 

their  aptitude  for  entering  into  combination?  For  instance,  the  princi- 
pal mineral  substances  found  in  goitengenous  waters  are  salts  of  lime 
and  magnesium.  In  the  Alps  goitengenous  waters  may  frequently  be 
distinguished  from  others  by  their  calcareous  deposits.  But  as  these 
same  mineral  salts  are  also  found  in  equal  quantities  in  other  waters 
which  are  manifestly  not  goiterigenous  a  causal  influence  cannot  be 
attributed  to  them  unless  m  these  native  or  plutonic  waters  some 
unknown  constituent  might  alter  their  action  in  the  human  organism. 
Possibly  the  energy  developed  by  the  disintegration  of  radio-active 
bodies  has  been  employed  in  some  abnormal  biochemical  process. 

In  short,  Repin  attributes  capital  importance  to  the  chemical  ingre- 
dients of  goiterigenous  waters,  especially  salts  of  lime  or  magnesium,  in 
combination  with  radio-active  substances.  He  bases  this  hypothesis  upon 
the  works  of  Senator,  Leopold-Levi,  de  Rothschild,  Hertoghe  and  others 
who  have  proved  that  the  function  of  the  thyroid  is  not  single  but  is 
multiple.  •  One  function  controls  the  secretion  of  iodin,  upon  which 
depends  the  general  metabolism;  another  function  controls  the  secretion 
of  phosphorus,  which  in  turn  presides  over  the  thermogenesis,  the  vaso- 
motricity,  and  the  regulation  of  the  cardiac  rhythm;  another  function 
controls  the  secretion  of  sulphur,  upon  which  depends  the  nutrition  of 
the  skm  and  hair;  another  function  controls  the  secretion  of  arsenic,  to 
an  insufficiency  of  which  Hertoghe  attributes  attacks  of  migraine.  Each 
one  of  these  functions  is  exercised  by  means  of  a  special  hormone  which 
is  secreted  by  a  distinct  mechanism,  so  that  in  fact  the  thyroid  gland 
is  composed  of  a  bunch  of  separate  glands  intimately  associated  and 
interwoven. 

It  will  be  easily  conceived  that  when  any  of  these  functions  is  over- 
excited, one  or  more  of  the  others  is  liable  to  become  disordered. 

In  this  connection  Repin  considers  that  the  discoveries  of  Sabatani, 
J.  Loeb  and  his  school  as  to  the  biological  action  of  the  calcium  ion  are 
particularly  valuable.  These  physiologists  have  shown  that  the  cal- 
cium ion  is  a  moderator  of  the  cellular  functions.  Augmentation  of  the 
protoplasmic  concentration  of  the  calcium  ion  is  accompanied  by  depres- 
sion, while  diminution  of  the  concentration  occasions  phenomena  of 
excitement.  The  thyroid  gland  is  the  regulator  of  the  metabolistic 
mechanism  of  the  calcium  ion  and  its  opposing  sodium  ion.  The  influ- 
ence of  decalcifying  agents,  and  especially  sodium,  is  exactly  opposed 
to  that  of  salts  of  lime.  Now,  the  work  of  Senator,  Moraczewski, 
Papinian,  Leopold-Levi,  de  Rothschild  and  others  has  established  that 
the  thyroid  gland  controls  the  metabolism  of  lime,  and  Repin  holds  it 
possible  that  in  exercising  its  functional  control  over  tin-  general  metab- 
olism the  thyroid  gland  may  modify  the  concentration  of  the  calcium 
ion  and  the  sodium  ion. 


262  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

This  much  granted,  Repin  suggests  an  hypothesis  which  would 
cover  all  sides  of  the  problem.  Suppose  that  the  calcium  ions  of  goiter- 
igenous  waters  differ  from  those  contained  in  ordinary  solutions  by  some 
one  property — perhaps  of  an  electrical  character — and  because  of  this 
difference  are  not  subject  in  the  same  degree  to  the  osmotic  law,  and 
are  more  readily  diffused  in  the  cytoplasm,  where  they  remain  in  a 
higher  state  of  concentration.  In  this  case  the  ingestion  of  goiterigenous 
waters  would  induce  a  condition  of  hypercalcification  from  which  would 
ensue  a  depression  in  the  general  metabolism.  The  effect  would  be  that 
of  a  mineral  water  chemically  characterized  by  a  dominant  lime  and 
physiologically  by  a  depression  of  the  metabolism.  These  waters  might 
be  classified  as  the  antagonists  of  those  having  a  dominant  of  sodium, 
and  in  this  connection  it  is  interesting  to  recall  the  statement  of  Leopold- 
Levi  and  de  Rothschild  that  patients  who  have  taken  the  cure  at  Aix 
sometimes  show  symptoms  of  Basedowism.  Because  of  the  hypercon- 
centration  of  the  calcium  ion,  the  thyroid  gland  is  obliged  to  augment 
its  secretion  in  order  to  maintain  the  chemical  balance  of  the  organism; 
hence  hyperplasia  of  the  gland,  and  if  the  use  of  water  containing  the 
injurious  ingredient  is  continued,  the  gland,  being  unable  to  increase 
its  secretion  in  sufficient  quantity  to  compensate  for  the  hypercalcifica- 
tion, symptoms  of  hypothyroidism  are  added  to  the  already  existing 
enlargement. 

E.  Bircher  remarks  that  these  conclusions  as  to  the  biophysiological 
action  of  the  goiterigenous  waters  in  the  organism  must  be  considered 
as  hypothetical  in  view  of  the  fact  that  the  metabolism  of  lime  is  con- 
trolled by  the  parathyroids  and  not  by  the  thyroid  gland  itself. 

Repin  suggests  that  these  facts  might  serve  as  a  basis  for  a  new 
treatment  of  hyperthyroidism.  The  tendency  of  goiterigenous  waters 
being  certainly  to  reduce  the  secretion  of  thyroiodin,  he  believes  they 
might  be  successfully  employed  in  combating  the  hypersecretion  of 
exophthalmic  goiter.  In  support  of  this  theory  he  cites  a  case  reported 
by  Prof.  Wilms,  of  Basel,  of  a  patient  suffering  from  exophthalmic  goiter 
whose  condition  invariably  improved  while  living  in  endemic  territory. 

Radio-active  Waters  and  Goiter. — Although  radium  has  been  used 
therapeutically  in  the  human  organism,  and  experimentally  on  animals, 
and  although  it  has  been  recognized  that  according  to  dose  and  methods 
of  application,  disturbances  to  health  may  ensue  therefrom,  and  although 
mice,  guinea-pigs,  and  frogs  have  been  killed  by  breathing  air  contain- 
ing radium  emanations  in  large  quantities  (several  million  mache  units 
to  the  liter),  it  has,  notwithstanding  this,  never  been  found  that  an 
enlargement  of  the  thyroid  could  be  attributed  to  the  use  of  radium  in 
any  form.  Further  evidence  in  this  direction  is  furnished  by  the  large 
industrial    class    employed    in    handling  highly  radio-active    substances. 


THEORIES  REGARDING  THE  ETIOLOGY  OF  GOITER  263 

Prof.  Dr.  Hahn  of  the  Chemical  Institute  of  the  University  of  Berlin, 
who  has  worked  with  radium  for  six  years,  declares  that,  although  con- 
stantly occupied  in  an  atmosphere  containing  radium  emanations, 
exceeding  the  therapeutic  dose  a  million  times,  he  has  never  observed 
or  heard  of  a  goiter  thus  produced. 

In  Saxony  there  are  certain  districts  where  the  endemic  prevails 
with  greater  intensity  than  elsewhere  and  this  is  particularlv  the  case 
in  Eastern  Vogtland  and  Western  Erzgebirge.  Hesse  finds  that  oro- 
graphically  considered  the  well-defined  endemic  may  be  said  to  prevail 
only  in  the  high  mountainous  parts  of  the  kingdom  while  the  plains  are 
relatively  free. 

The  exceedingly  varied  surface  of  the  land  is  naturally  accompanied 
by  an  unusual  wealth  of  geological  formations  due  to  great  volcanic 
activity  in  the  earlier  phases  of  the  world's  history.  It  is  therefore 
not  astonishing  that  valuable  minerals  and  metals  should  be  found 
there  in  abundance.  Large  quantities  of  uranium  minerals  are  also 
present,  and  because  of  the  amount  of  radium  contained  in  these 
minerals,  the  interest  of  those  technically  concerned  with  these 
products  has  been  aroused  so  that  investigations  have  been  made  con- 
cerning them.  Springs  and  wTaters  were  tested  as  to  their  radio-activity 
by  order  of  the  Kgl.  Sach's.  Finanzministenum,  and  thus  it  was  found 
that  Saxony  possessed  radio-active  springs,  and  that  some  of  these  waters 
contain  the  highest  amount  of  radium  that  has  as  yet  been  measured. 

The  results  of  these  examinations  placed  at  Hesse's  disposition  a 
considerable  mass  of  reliable  material  for  the  comparative  study  of 
local  correlations  between  radio-active  waters  and  goiter.  His  conclu- 
sions are  that  the  goiter  endemic  prevails  most  frequently  in  high-lying 
mountainous  countries,  and  that  here  because  of  certain  geological  and 
mineralogical  conditions  strong  radio-active  waters  are  found  in  great 
numbers,  but  that  such  waters  are  as  frequently  found  and  are  of  equal 
strength  where  goiter  is  unknown.  It  may  be  concluded  that  there  is  no 
causal  connection  between  radio-activity  and  goiter,  and  that  the  parallel 
coincidence  of  radio-active  water  and  endemic  goiter  is  accidental  and 
not  regular. 

Organic  Theory. — Prof.  Wilms  is  of  the  opinion  that  goiter  is  due  to 
an  organic  ferment.  These  views  are  based  upon  Bircher's  experiments 
with  goiterigenous  water  upon  rats.  \\  llms  thinks  it  impossible-  that  a 
living  organism  should  be  confined  to  certain  geological  formations,  and 
came  to  the  following  conclusions: 

During  the  formative  process  of  the  marine  sedimentary  strata,  sea 
fauna  must  necessarily  have  been  included  in  these  deposits  which  are 
therefore  highly  impregnated  with  organic  substances.  It  is  not  improb- 
able that  water  running  through  these  sedimentary  strata  would  wash 


264  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

out  and  carry  off  in  solution  some  of  the  products  of  decomposition 
from  these  organic  substances.  The  presence  of  these  products  in  the 
water  as  toxin  or  organic  ferments  might  then  act  as  the  exciting  cause 
of  endemic  goiter.  Wilms  thinks  that  strong  evidence  in  favor  of  this 
theory  is  furnished  by  Bircher's  experiments  proving  that  goiter  can  be 
produced  in  rats  by  water  which  has  passed  through  the  Berkefeld 
filter,  and  by  Wilm's  own  investigations  which  have  established  that 
goiterigenous  water  when  heated  to  Jo°  loses  its  harmful  properties, 
this  being  the  temperature  at  which  toxins  and  ferments,  especially 
toxalbumins,  are  rendered  innocuous.  From  these  facts  Wilms  con- 
cludes that  the  cause  of  goiter  must  be  due  to  a  toxin  rather  than  to  an 
organic  excitant,  and  that  this  toxin  is  held  in  solution  in  the  drinking 
water.     Bircher  believes  the  toxin  to  be  of  colloidal  nature. 

Dr.  Sasaki,  acting  upon  Prof.  Wilm's  suggestion,  made  a  series  of 
experiments  with  the  view  of  studying  the  action  of  organic  poisons  in 
the  production  of  goiter.  These  experiments  carried  out  by  Dr.  Sasaki 
at  Heidelberg  gave  the  following  results: 

i.  By  feeding  animals  on  cooked  rice  mixed  with  rat  feces,  moderate 
sized  enlargement  of  the  thyroid  gland  of  a  diffuse  character  was 
produced. 

2.  Feeding  with  decayed  fish  gave  negative  results.  The  animals 
died   rapidly  and  showed   disturbances  in  growth. 

3.  By  feeding  with  decayed  meat,  negative  results  were  produced. 

4.  Feeding  with  calves'  thymuses  also  gave  negative  results. 

5.  Subcutaneous  injections  with  cadaverous  products  in  large  and 
small  doses  gave  negative  results.     The  animals  died  soon. 

6.  Subcutaneous  injections  of  tyrosin  also  gave  negative  results. 

7.  Subcutaneous  injections  of  acetonetnle  gave  negative  results. 

8.  Feeding  with  rat  feces  mixed  with  iodide  of  potassium  also  gave 
negative  results. 

9.  Feeding  with  rat  feces  mixed  with  thyroidin  produced  negative 
results. 

These  findings  are  exceedingly  interesting  and  valuable  as  they  show 
that  organic  poisons  are  not  capable  of  producing  goiter,  but  that  fecal 
matter  contains  a  substance  which  may  cause  alterations  in  the  thyroid 
gland  when  introduced  into  the  circulation.  Moreover,  the  addition  of 
small  quantities  of  potassium  iodide  or  thyroidin  to  food  which  has 
been  mixed  with  fecal  matter  was  sufficient  to  prevent  goiterous  changes 
from  taking  place  in  the  thyroid  gland.  All  of  these  observations  cor- 
roborate McCarrison's  findings  and  coincide  with  the  observations  upon 
the  retrogression  of  goiter  among  fish,  after  the  addition  of  small  quan- 
tities of  antiseptics,  sublimate  of  potassium  iodide  (solution  1  to  5,000,000) 
to  the  water  of  the  fish  tanks. 


THEORIES  REGARDIXG  THE  ETIOLOGY  OF  GOITER  265 

Interesting  in  this  connection  are  the  experiments  of  Dr.  Fr.  Messerli, 
of  Lausanne  (Revue  Medicale  de  la  Suisse  Romande,  March  20,  191 5), 
in  the  treatment  of  goiter  by  intestinal  disinfection.  The  disinfectants 
used  by  him  were  thymol,  benzonaphthol,  salol,  creosote  pills,  and  mild 
laxative  pills,  the  effect  of  which  was  merely  to  reduce  the  bacterial 
flora  of  the  intestines  by  evacuation.  In  the  11  cases  subjected  to  these 
different  therapeutic  measures  the  results  were  surprisingly  good  and 
have  convinced  Dr.  Messerli  that  endemic  goiter  is  coincident  with  the 
use  of  drinking  water  which  in  some  way  has  been  exposed  to  parasitic 
pollution.  He  does  not  know  whether  to  attribute  the  results  obtained 
from  the  antiseptic  treatment  to  a  direct  action  upon  the  specific  goiter 
agent  in  the  intestines  or  to  a  general  effect  in  diminishing  the  number 
of  normal  microbes  in  the  intestines  and  thus  decreasing  their  toxic 
products. 

These  various  experiments  establish  clearly  that  the  goiter  agent, 
whether  living  organism  or  toxin,  is  inhibited  in  its  activity  by  the  use 
of  disinfectants. 

Probably  this  restraining  influence  consists  in  a  cooperative  action 
with  the  thyroid  gland  by  means  of  which  it  is  enabled  to  accomplish 
its  normal  task  of  counteracting  and  overcoming  the  ferments  always 
present  in  the  intestine,  and  at  the  same  time  to  combat  the  specific 
goiter  toxin.  Such  little  assistance  is  sufficient  to  enable  the  gland  to 
do  all  of  this  task  without  overwork  which  results  in  hypertrophy,  or 
in  failure  to  accomplish  the  whole  task,  from  which  ensues  the  injurious 
and  progressive  accumulation  of  toxins  resulting  in  goiter-heart  and 
other  phenomena  of  goiterous  degeneration. 

It  must,  however,  always  be  borne  in  mind  that  no  medical  treat- 
ment is  efficacious  in  cases  of  goiter  of  long  standing,  where  severe 
degenerative,  cystic,  and  adenomatous  changes  have  occurred.  In  all 
such  cases  there  is  no  other  recourse  than  to  surgical  treatment  which 
should  be  obtained  at  the  earliest  possible  date. 

Contagion  by  Contact  Theory. — On  account  of  long  years  of  personal 
experience  and  investigations  in  Styria  and  Tyrol,  Dr.  Adolph  Kutschera 
holds  that  the  theory  of  the  water  etiology  of  goiter  and  cretinism 
is  untenable.  He  is  convinced  that  the  only  reasonable  explana- 
tion of  the  various  characteristics  of  the  endemic  lies  in  contagion 
by  contact,  and  that  there  is  no  analogy  in  medical  experience  for 
the  generally  accepted  opinion  that  the  cause  of  goiter  is  to  be  sought 
only  in  the  drinking  water.  In  all  of  those  diseases,  he  continues,  the 
dissemination  of  which  was  for  a  long  time  attributed  to  water,  it  has 
ultimately  developed  that  water  was  not  the  principal  earner  of  the 
infection.  For  instance,  in  typhoid  fever,  dysentery,  and  cholera,  watei 
was  supposed  to  be  the  exclusive  source  of  the  evil  until  it  was  clearly 


266  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

established  that  the  principal  means  of  transmission  was  through  con- 
tagion by  contact.  Dr.  Kutschera  therefore  assumes  that  such  will 
be  the  case  for  goiter  and  for  cretinism  just  as  it  has  been  for  the  fore- 
going diseases. 

Before  entering  into  the  reasons  which  have  brought  him  to  this 
conclusion,  the  author  defines  his  conception  of  cretinism  in  order  to 
make  clear  the  basis  upon  which  he  founds  his  theory  as  to  the  common 
etiology  of  these  disturbances.  This  conception  is  based  upon  etiologi- 
cal reasons,  and  not  upon  clinical  observations,  and  includes  all  of  the 
developmental  disturbances  both  physical  and  mental  which  are  caused 
by  the  cretinogenous  noxa  in  endemic  territory.  Varying  as  this  pic- 
ture does  from  normal  to  the  severest  forms  of  hypothyroidism,  idiocy, 
and  deaf-mutism,  all  of  these  disturbances  can  be  traced  to  the  same 
original  cause.  Goiter  must,  he  declares,  be  included  in  these  disturb- 
ances, but  it  bears  a  peculiar  relationship  to  them;  its  general  distri- 
bution is  far  wider  than  that  of  cretinism  and  outside  of  regions  where 
endemic  goiter  prevails  there  is  no  cretinism.  Cretinoid  children,  he 
continues,  almost  invariably  have  goiterous  mothers,  and  in  the  rare 
cases  where  this  is  not  true,  either  the  father  or  another  member  of  the 
family  will  be  found  to  have  goiter. 

The  most  constant  injury,  adds  Kutschera,  that  can  be  traced 
through  all  of  the  various  disturbances  occasioned  by  the  endemic  noxa 
is  not  goiter,  but  injury  to  the  nervous  system.  The  endemic  noxa  acts 
upon  the  nervous  system  especially,  and  the  seventy  of  the  disturbances 
occasioned  are  determined  by  the  power  of  resistance  in  the  individual 
attacked.  The  younger  the  child  exposed  to  these  influences,  the  more 
liable  will  it  be  to  acquire  severer  forms  of  the  disease  as  idiocy  and 
deaf-mutism;  while  in  adults  and  older  children  the  result  will  be 
endemic  goiter  and  its  accompanying  symptoms.  Kutschera  recalls 
that  the  thyroid  gland  is  peculiarly  susceptible  to  nervous  influences, 
as  has  been  shown  in  exophthalmic  goiter,  and  he  concludes  that  the 
goiterous  agent  works  through  the  nervous  system  upon  the  thyroid 
gland,  occasioning  the  cretinous  degeneration  when  attacking  the  fetus 
or  newborn  child,  and  causing  goiter  in  the  adult,  or  more  resistant 
body.  Kutschera  continues  his  arguments  by  showing  that  the  general 
opinion  that  goiter  and  cretinism  are  confined  to  certain  districts  has 
been  shown  to  be  erroneous,  and  that  this  assumption  was  largely  due 
to  the  exquisitely  chronic  nature  of  the  disease  which  lasted  a  whole 
lifetime;  its  fluctuations  covering  decades  and  centuries  instead  of  weeks 
or  months  as  in  ordinary  diseases.  Cavatorti  (1907)  further  illustrates 
that  in  Italy  goiter  has  entirely  disappeared  from  the  Provinces  of 
Ferrara,  Bari,  and  certain  districts  of  Sicily,  and  that  many  other 
investigators    report    the    endemics    of    both    goiter   and    cretinism    as 


THEORIES  REGARDING   THE  ETIOLOGY  OF  GOITER  267 

diminishing  or  gone  from  localities  where  the)'  formerly  prevailed. 
Even  more  significant  than  these  local  and  periodical  fluctuations  of  the 
endemic  he  finds  the  fact  that  goiter  and  cretinism  are  not  evenly  dis- 
tributed among  the  inhabitants  in  endemic  territory  as  would  be  the 
case  were  water  the  only  cause  of  the  disease.  Dr.  Kutschera  concludes 
that  careful  examinations  of  all  individuals  living  in  groups  of  houses 
having  a  common  water  service  show  clearly  that  goiter  and  cretinism 
are  not  dependent  upon  the  community  of  water,  but  are  confined  to 
certain  houses,  and  in  large  tenement  houses  may  be  traced  to  certain 
dwellings,  i.  e.,  it  is  a  house  disease  like  tuberculosis. 

Although  cretinism  is  a  pronounced  family  disease  it  cannot  be  con- 
sidered hereditary  inasmuch  as  the  parents  of  cretins  are  in  general 
normal  except  that  the  mother  in  almost  all  cases  has  a  goiter.  Children 
of  cretinous  mothers  may,  and  often  do,  develop  normally  if  removed 
to  a  neighboring  house  where  there  is  no  goiter  or  cretinism.  Kostl 
observed  in  1855  that  among  the  noblemen  of  the  Canton  of  Valais  it 
was  customary  to  bring  up  only  the  eldest  son  at  home  while  the  others 
were  left  to  the  care  of  cretinous  servants  and  likewise  became  cretins 
themselves.  The  necessity  of  dividing  the  property  among  so  many 
children  was  thus  avoided. 

Kutschera  bases  his  theor\r  that  goiter  and  cretinism  in  endemic 
territory  are  confined  to  certain  dwellings,  upon  investigations  made  in 
nearly  two  hundred  localities  where  he  always  found  homes  inhabited 
by  cretins  grouped  together  in  close  vicinity. 

He  did  not  find  it  possible  to  establish  a  correlation  between  the 
common  water  supply  and  the  disease,  as  one  and  the  same  water  was 
used  in  the  cretin  houses  and  in  those  free  from  the  disease.  Where 
one  cretin  was  found,  there  were  usually  others  in  the  house,  and  it  was 
frequently  shown  that  the  house  had  formerly  been  occupied  by  cretins. 
Kutschera  emphasizes  this  point  in  the  hope  that  these  conditions  may 
be  investigated  in  other  localities.  In  1844  Fradeneck  described  the 
Tostenhuben  in  the  community  of  Sirnitz,  Carinthia,  where  from  time 
immemorial  all  children  and  adults  suffered  from  the  cretinous  degen- 
eration, lhese  Tostenhuben  which  still  exist  were  recently  visited  b\ 
Kutschera,  who  was  unable  to  find  either  goiter  or  cretinism  at  the 
present  time.  Two  of  these  Tostenhuben  had  been  destroyed  by  fire 
and  rebuilt.  One  had  remained  unoccupied  during  forty  years  and  was 
then  refurnished.  Goiter  and  cretinism  have  since  disappeared.  In 
one  of  these  "huben"  which  burned  down  in  1847  it  was  ascertained 
that  a  child  born  before  the  fire  was  still  cretinous,  while  all  the  children 
born  since  the  fire,  among  whom  is  the  present  proprietor,  have  devel- 
oped normally.  I  he  water  supply  in  every  instance  has  remained 
unchanged. 


268  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

Since  the  water  cannot  have  been  the  cause  of  goiter  and  cretinism 
it  must  be  assumed,  Kutschera  thinks,  that  the  disease  was  transmitted 
by  means  of  the  household  furnishing,  bedding,  clothing,  etc. 

The  occurrence  of  goiter  and  cretinism  outside  of  endemic  territory 
furnishes  further  evidence  in  favor  of  contagion  by  contact.  Kutschera 
recently  encountered  an  unusually  typical  twenty-year-old  cretin  in  a 
part  of  Tyrol  (the  district  of  Brixen),  where  goiter  is  rare  and  cretinism 
unknown.  Investigations  showed  that  all  the  members  of  the  household 
including  mother,  sister,  and  two  little  children  boarding  with  the 
family,  were  goiterous.  Further  instances  are  given  where  in  immune 
territory  entire  families  may  be  found  with  goiter,  the  mother  being  a 
goiter-bearer  from  a  region  where  the  endemic  prevails.  Kutschera 
considers  the  already  cited  endemic  in  Deoba,  India,  where  the  Brahmin 
class  remained  immune  as  due  to  their  complete  isolation,  and  the  con- 
sequent protection  from  infection  by  contact  rather  than  to  the  differ- 
ence in  water  supply  to  which  it  is  attributed  by  McClelland. 

Kutschera  asserts  that  so-called  goiter  wells  will  not  bear  investiga- 
tion. The  stories  of  military  conscripts  having  acquired  goiter  by 
drinking  from  wells  in  endemic  territory  is  to  be  explained  by  their 
living  with  goiterous  families  where  the  disease  was  transmitted  by  con- 
tact. According  to  his  views  all  goiter  epidemics  are  to  be  considered 
as  evidence  against  the  water  etiology  of  goiter,  as  they  never  attack 
those  having  a  common  water  supply,  but  are  always  confined  to  some 
one  house  or  dwelling  such  as  barracks,  boarding  schools,  etc. 

The  endemics  in  fish  ponds  cited  by  Gaylord  are  also  given  as  ex- 
amples of  infection  by  contact.  Positive  animal  experiments  in  endemic 
territory  are  explained  by  the  animals  being  exposed  to  contagion  by 
contact.  In  closing  Kutschera  refers  to  Chagas'  disease  in  Brazil  which 
in  its  chronic  forms  resembles  cretinism  and  is  transmitted  from  man 
to  man  by  the  bite  of  an  insect.  Kutschera  thinks  the  discovery  of  this 
disease  to  be  of  the  greatest  importance  for  the  etiology  of  endemic 
goiter  and  cretinism.  Analogy  is  of  such  moment  in  medical  matters 
that  the  possibility  of  the  transmission  of  these  endemic  diseases  through 
some  intermediary  host  must  be  at  least  considered. 

The  fact  that  the  development  of  goiter  and  cretinism  is  favored  by 
unhygienic  living  might  indicate  the  intervention  of  some  species  of  insect. 

Dr.  Siegmund  Taussig's  researches  concerning  goiter  and  cretinism 
in  Bosnia  have  led  him  to  form  the  same  conclusions  as  Dr.  Adolph 
Kutschera  concerning  the  infectious  origin  of  goiter.  Cretinism  he 
believes  to  be  a  congenital  condition  due  to  goiter  in  the  mother.  In 
Bosnia  and  Herzegovina  the  opportunities  to  observe  the  dissemination 
of  infectious  diseases  by  contact  are  numerous  because  of  the  customs 
and  habits  prevailing  among  the  population. 


THEORIES  REGARDIXG  THE  ETIOLOGY  OF  GOITER  269 

Through  his  observations  in  Bosnia  Kobler1  became  convinced  that 
leprosy  is  transmitted  by  contact;  moreover,  it  is  noteworthy  that  in 
Bosnia  leprosy  is  seldom  found  in  large  cities;  that  it  attacks  by  prefer- 
ence the  masculine  sex  (83  per  cent.)  and  that  44  per  cent,  of  those 
attacked  are  Mohammedans.  (The  latter  constitute  32  per  cent,  of  the 
population.)  The  dissemination  of  syphilis  in  Bosnia  has  likewise 
attained  most  unusual  proportions. 

A  recent  governmental  investigation  showed  not  less  than  42,000 
cases  of  syphilis,  the  great  majority  of  which  were  extragenital.  A 
high  percentage  of  the  Mohammedan  population  was  affected  in  this 
case  also.  These  observations  and  his  own  experience  as  to  the  repeated 
occurrence  of  goiter  in  families  brought  the  author  to  the  conclusion 
that  Kutschera's  theory  offered  a  possible  solution  of  the  goiter  prob- 
lem. From  this  point  of  view  Dr.  Taussig  carried  out  extensive 
researches  in  Bosnia,  especial  emphasis  being  laid  on  family  histories  as 
a  point  most  important  for  the  contact  theory. 

The  customs  of  these  people  are  peculiarly  favorable  for  the  trans- 
mission of  disease  by  contact.  The  population  is  almost  entirely  of  the 
agricultural  class  whose  custom  is  to  prepare  and  serve  their  food  in  a 
common  vessel  from  which  each  takes  his  portion  without  the  formality 
or  the  intervention  of  forks,  spoon,  or  plates.  Cups  and  glasses  are  like- 
wise rare.  The  drinking  water  is  kept  in  an  earthenware  jar  from  which 
all  members  of  the  household  drink.  Beds  are  almost  unknown;  every- 
one sleeps  on  the  floor — members  of  the  family  side  by  side,  in  the  same 
room.  These  primitive  customs  are  more  prevalent  in  isolated  and 
inaccessible  localities,  and  are  always  accentuated  in  the  Mohammedan 
families  who  cling  to  their  old  traditions  with  obstinate  conservatism 
and  accept  modern  customs  with  difficulty,  whereas,  modern  hygienic 
conceptions  have  been  more  rapidly  absorbed  by  the  Christian 
population. 

Dr.  Taussig's  own  observations  rest  upon  these  facts.  In  the  garri- 
son of  130  men  at  Srebrenica  there  has  never  been  a  case  of  goiter.  It 
is  true  that  the  garrison  has  a  water  supply  of  its  own,  but  this  is 
obtained  from  the  Bojnagebirge  whence  the  civilian  population  also 
draws  its  water  supply.  Among  the  families  of  officials  and  officers  who 
have  lived  in  Srebrenica  for  years  and  were  scattered  throughout  the 
city,  there  was  no  goiter,  with  the  single  exception  of  one  child  who 
attended  the  public  schools.  Although  the  Austrian  police  are  dis- 
persed throughout  the  district,  goiter  is  unknown  among  them.  Dr. 
Taussig  concludes  that  for  the  development  of  goiter  there  must  be 
opportunity  for  repeated  and  close  contact  or  association,  and  this  being 

1  Ueber  chis  Vorkommen und  Bekampfung der  Lepra  in  Bosnia  und  Herzegovina,  iwio. 


270  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

precluded   by   the   religious   and    social   differences   between   the   native 
and  foreign  population,  the  endemic  is  not  transmitted. 

In  the  community  of  Gladovic  where  the  endemic  is  intense  there 
is  an  isolated  group  of  houses  entirely  free  from  goiter  and  cretinism, 
although  drawing  its  water  supply  from  the  same  source  as  the  rest  of 
the  community.  Sarajevo,  the  largest  city  of  Bosnia,  is  in  general  free 
from  goiter  and  cretinism,  although  isolated  goiters  are  to  be  found 
among  the  older  inhabitants.  Neither  in  the  garrison  of  4000  men  nor 
in  the  families  of  officers  and  officials  is  goiter  of  frequent  occurrence. 

In  the  course  of  his  investigations  Dr.  Taussig  was  informed  that 
where  goiter  was  contracted  among  the  families  of  foreigners  settled  in 
Sarajevo,  some  one  member  of  the  family  has  first  acquired  the  disease, 
the  others  becoming  infected  one  after  the  other. 

Dr.  Taussig  reports  an  interesting  case  which  he  considers  has  the 
value  of  an  experiment  in  support  of  Kutschera's  theory.  On  June  30, 
191 1,  a  fox  terrier  bitch  owned  by  an  army  officer  gave  birth  to  3  pups 
of  which  2  were  males.  Nothing  unusual  was  noticed  in  the  pups  until 
August  7,  when  all  three  developed  a  swelling  in  the  throat  which  was 
pronounced  goiter  by  the  veterinary  consulted. 

When  told  of  this  occurrence,  the  author  immediately  asserted  that 
these  dogs  had  been  infected  by  some  one  living  in  the  house.  Exami- 
nation of  every  member  of  the  household  showed  that  the  members 
of  the  officer's  family  were  free  from  goiter.  But  the  cook,  who  had  been 
living  in  the  family  for  two  years,  had  a  slight  swelling  of  the  thyroid 
gland,  and  the  orderly,  who  was  entering  upon  his  third  year  of  ser- 
vice, had  a  well-developed  goiter  which  he  had  heretofore  concealed  by 
his  clothing.  This  orderly  had  charge  of  the  dogs  which  Dr.  Taussig 
believes  had  been  infected  by  him  as  had  the  cook  who  came  from 
immune  territory  and  was  unaware  of  her  thyroid  enlargement. 

Epidemics  observed  in  Bosnia  and  elsewhere,  he  finds,  are  always 
confined  to  members  of  the  same  household,  the  rest  of  the  community, 
although  drinking  the  same  water,  remaining  unaffected. 

Animal  experiments  are  not  conclusive  because  ordinarily  carried 
out  in  endemic  territory,  and  contradictory,  opposite  results  are  fre- 
quently obtained  by  different  investigators.  The  fact  that  in  Gaylord's 
interesting  observations  of  goiter  among  fish,  the  addition  of  an  infinitesi- 
mal quantity  of  potassium  iodide  or  sublimate  to  the  water  was  suffi- 
cient to  occasion  retrogression  of  the  goiter  indicates  a  parasitic  origin 
of  the  disease.  Dr.  Taussig  reports  that  in  his  examinations  of  cretinous 
individuals  he  made  special  inquiries  as  to  the  domestic  animals  and  was 
never  able  to  discover  a  single  case  of  goiter  or  cretinism  among  them. 
Acting  upon  the  assumption  that  the  goiter  virus  is  in  the  saliva,  Dr. 
Taussig  experimented   upon   a   young  guinea-pig  and   a   young  dog  by 


THEORIES  REGARDIXG  THE  ETIOLOGY  OF  GOITER  271 

mixing  the  saliva  of  cretins  with  their  food.  Both  animals  died  within 
a  few  weeks,  but  the  postmortem  examination  showed  no  enlargement 
of  the  thyroid  gland. 

Dr.  Taussig  sees  a  parallel  case  in  the  wide  distribution  of  syphilis 
throughout  Bosnia  where  the  general  investigations  made  by  the  Gov- 
ernment established  the  fact  that  the  transmission  of  the  disease  was 
due  to  the  use  of  common  eating  and  drinking  utensils,  the  primary 
and  secondary  lesions  occurring  in  the  mouth.  Dr.  Taussig  concludes 
that  endemic  goiter  is  transmitted  in  the  same  way.  The  fact  that  the 
disease  is  commoner  in  the  Moslem  than  in  the  Christian  population  is 
further  evidence  in  this  direction  because  of  the  obstinate  adherence  of 
the  former  to  their  primitive  customs  and  unhygienic  habits  of  living. 

Dr.  Taussig  finds  a  marked  association  between  goiter  immunity 
and  the  use  of  sea-salt.  Countries  which  are  either  free  from  the  endemic 
disease,  or  where  goiter  is  rare,  use  sea-salt.  This  immunizing  property 
is  to  be  attributed  to  the  iodin  in  the  sea-salt,  the  constant  ingestion  of 
which  in  such  minute  and  easily  absorbed  quantities  is  sufficient  to 
increase  the  iodin  supply  of  the  thyroid  gland  and  thus  to  destroy  the 
goiter  virus.  Dr.  Taussig  believes  that  sea-salt  is  destined  to  play  an 
important  part  in  the  prevention  and  cure  of  goiter,  as  it  possesses  the 
immense  advantage  over  all  other  therapeutic  measures  of  being  easily 
available  for  all  classes,  and  furthermore,  that  its  use  may  be  prolonged 
indefinitely  without  any  ill  result  or  disturbance  of  any  kind. 

Dr.  Taussig  is  unable  to  accept  Kutschera's  theory  that  cretinism 
is  acquired  simply  by  contact.  His  researches  in  Bosnia  and  Tyrol 
have  convinced  him  that  cretinism  is  always  congenital,  but,  as  the 
condition  is  difficult  of  diagnosis  in  a  young  infant,  it  ordinarily  escapes 
notice  until  the  child  is  a  year  or  more  old.  The  best  proof  that  the 
cretinogenous  injury  must  have  taken  place  in  atero  is  to  be  found  in  the 
several  cases  of  cretin  twins  examined  by  Taussig  in  Bosnia  and 
Herzegovina  and  by  Cerletti  and  Perusini  in  Italy;  in  each  case  the 
clinical  picture  was  the  same  in  nature  and  degree  for  both  twins. 

Taussig's  conclusions  are  that  without  goiter  in  the  mother  there  is 
no  cretinism.  The  mother  who  has  been  infected  by  the  goiter  virus 
has  been  injured  in  her  reproductive  power  and  consequently  is  fre- 
quently subject  to  miscarriage,  premature  birth,  or  the  child  is  not 
viable.  The  children  that  survive  are  cretins.  In  time  these  manifes- 
tations become  less  severe,  and  the  last  children  are  usually  in  better 
physical  condition.  Nature  seems  to  exercise  an  autoprotecti  ve  pro- 
cess, the  goiter  virus  and  its  injurious  effects  being  ultimately  counter- 
acted in  the  system. 

Dr.  Taussig  acknowledges  that  these  very  unusual  phenomena  are 
remarkably   like  what  we   know  of  syphilis,   but   he   affirms   that  these 


272  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

observations  were  made  not  only  in  Bosnia  where  syphilis  is  so  widely 
distributed,  but  also  in  Styria  and  Tyrol,  and  that  in  the  family  histories 
taken  by  himself  and  the  statistics  consulted  there  was  no  syphilis. 

There  is  no  analog)'  between  these  findings  of  Taussig's  and  the 
conditions  existing  in  regions  of  high  endemicity  in  Switzerland  where 
miscarriage  and  premature  delivery  are  not  unusually  frequent,  although 
the  rate  of  infant  mortality  is  higher  than  elsewhere.  Taussig  found  the 
results  obtained  in  the  treatment  of  cretinism  by  thyroid  opotherapy 
unsatisfactory.  Some  degree  of  physical  improvement  ensued  such  as 
increased  growth  and  lessening  of  the  myxedematous  symptoms,  but 
the  mental  condition  remained  unchanged,  any  apparent  improvement 
in  this  direction  being  due  to  reduction  in  the  myxedematous  swelling 
of  the  mouth  and  pharyngeal  cavity  so  that  the  child  is  enabled  to  hear 
and  speak  with  greater  ease.  He  found,  furthermore,  that  treatment 
with  thyroid  tablets,  although  continued  through  several  years,  resulted 
in  no  intellectual  improvement. 

Infection  Theory. — Dr.  Robert  McCarrison,  of  the  Indian  Medical 
Service,  in  his  Etiology  of  Endemic  Goiter  bases  his  conclusions  upon 
observations  and  experiments  made  during  ten  years'  residence  in  a 
part  of  India  where  endemic  goiter  prevails  with  great  intensity.  He 
has  further  verified  these  conclusions  by  studying  the  disease  in  the 
various  goiter  centers  of  Europe  and  is  convinced  that  the  endemic 
goiter  of  Europe  and  Himalayan  India  are  one  and  the  same  disease. 
He  believes  water  to  be  the  ordinary  means  of  conveying  the  toxic  agent 
of  endemic  goiter  and  bases  his  belief  upon  the  positive  results  of  his 
experiments  in  giving  young  men  the  residue  separated  by  filtration 
from  the  goitengenous  water  of  Kashrote,  and  upon  the  animal  experi- 
ments of  Bircher,  Marine,  Lenhardt  and  others.  The  toxic  nature  of 
the  waters  McCarrison  attributes  to  the  presence  in  suspension  of  a 
living  agent  which  is  the  direct  or  indirect  cause  of  the  disease. 

The  characteristics  of  goiter  produced  experimentally  in  man  are: 
i.   It  appears  about  the  fifteenth  day  of  the  experiment. 

2.  It  shows  a  marked  tendency  to  fluctuate  in  size. 

3.  It  reaches  its  maximum  in  size  between  the  twenty-fifth  and 

thirtieth  day  of  the  experiment. 

4.  The  enlargement  of  the  gland  is  neither  great  nor  progressive. 

5.  It  is  accompanied,  as  a  rule,  by  certain  subjective    symptoms 

as,  for  example,  throbbing  in  the  neck,  feelings  of  fulness  and 
discomfort. 

6.  It  may  completely  disappear  under  conditions  of  the  experiment. 
While  McCarrison  is  convinced  that  water  is  the  principal  means  of 

transmitting  the  contagium  vivum  of  goiter,  he  also  believes  that  the 
soil  may  become  a  vehicle.     An)'  soil,  no  matter  what  its  geological 


THEORIES  REGARDING  THE  ETIOLOGY  OF  GOITER  273 

formation,  may  be  converted  into  a  suitable  culture  medium  for  the 
living  excitant  of  goiter  through  the  presence  of  animal  or  vegetable 
matter.  It  is  not  the  pollution  of  the  soil  or  water  in  itself  that  is  the 
cause  of  goiter.  Just  as  polluted  water  will  not  cause  typhoid  fever 
unless  it  contains  the  Bacillus  typhosus,  so  a  polluted  water  will  not 
cause  goiter  unless  it  contains  the  living  excitant  to  which  the  disease 
is  due. 

McCarrison  believes  that  the  seat  of  the  infection  in  the  human 
bodv  is  the  intestinal  tract,  and  considers  that  he  has  demonstrated  the 
truth  of  this  view  by  the  results  obtained  in  the  treatment  of  endemic 
goiter  by  intestinal  antiseptics.  In  more  than  ioo  cases  in  which 
10  grs.  of  thymol  were  administered  night  and  morning,  the  greater 
number  were  either  entirely  cured  or  greatly  benefited. 

This  treatment  is  interesting  especially  because  of  its  etiological 
significance.  The  germicidal  power  of  thymol  is  very  great  and  McCar- 
rison believes  that  its  action  is  either  to  destroy  the  living  excitant  of 
the  goiter  in  the  intestine  or  so  to  reduce  its  numbers  and  activity 
that  the  production  of  toxic  substances  is  lessened  and  the  thyroid 
gland  thus  relieved  of  the  excessive  demand  for  its  counteracting  anti- 
toxic secretions. 

McCarrison  also  thinks  that  the  well-known  beneficial  action  of  10dm 
is  largely  due  to  its  germicidal  properties.  Further  evidence  as  to  the 
intestinal  location  of  the  goiter  infection  is  afforded  by  the  marked 
improvement  of  patients  treated  with  lactic  acid  ferments  (Bacillus  bul- 
garicus).  Remarkably  brilliant  results  were  also  obtained  by  the  use 
of  vaccines.  Having  observed  that  a  plentiful  amebic  infection  was 
present  in  the  intestinal  tract  of  sufferers  from  goiter  in  Gilgit,  McCarri- 
son endeavored  to  cultivate  these  organisms  and  was  struck  by  the 
constant  character  of  the  bacillary  growth  which  appeared  in  the  medium 
employed.  He  prepared  a  vaccine  from  these  bacteria  and  used  it 
experimentally  in  the  treatment  of  recent  cases  of  goiter.  No  attempt 
was  made  to  isolate  any  particular  organism.  The  vaccine  employed 
was  therefore  a  composite  one.  A  complete  cure  was  effected  in  both 
cases  where  the  vaccine  was  used.  It  was  then  noted  that  the  bacterial 
growth  referred  to  consisted  largely  of  a  bacillus  which  presented  the 
main  characteristics  of  the  coh  group.  A  vaccine  was  prepared  from 
this  bacillus,  resulting  as  before  in  a  complete  cure  of  the  patient 
treated.  Vaccines  were  then  made  from  bacteria  not  derived  from  the 
patient's  own  intestine.  A  staphylococcus  vaccine  prepared  from  a 
spore-bearing  organism  isolated  horn  the  feces  of  a  goiterous  pony  were 
used  successfully.  The  results  from  the  use  of  1*  orster's  dysenten 
vaccine  were  negative. 

Metchnikoff   has    discovered    that    certain    microbes   of   our    normal 
18 


274  ETIOLOGY  OF  ENDEMIC  GOITER  AND  CRETINISM 

intestinal  flora  are  harmful  by  reason  of  the  poisonous  substances — 
indol  and  phenol — to  which  they  give  rise  in  the  intestines.  Organisms 
of  the  coli  group,  the  staphylococcus,  and  certain  spore-bearing  organ- 
isms are  among  these  normal  inhabitants  of  the  intestines  which  are 
responsible  for  the  production  of  poisons,  and  the  injurious  action  upon 
the  liver,  kidneys,  and  arteries,  as  he  has  experimentally  demonstrated. 

Now  the  vaccines  employed  by  McCarnson  were  made  from  organ- 
isms similar  to  these,  and  as  there  is  no  evidence  at  present  that  any  of 
these  organisms  possess  a  specific  influence  in  the  production  of  goiter, 
McCarrison  explains  their  action  as  follows:  The  function  of  the  thy- 
roid gland  is  to  combat  the  poisons  normally  present  in  the  human  intes- 
tine, and  if  to  these  is  added  the  specific  virus  of  goiter,  the  gland  unaided 
cannot  suffice  to  counteract  all  these  toxins,  and  thus,  in  the  effort  to 
perform  its  normal  function  and  at  the  same  time  to  destroy  the  specific 
goiter  virus,  the  gland  frequently  undergoes  hypertrophy,  but  if  assisted 
in  any  one  direction,  it  is  capable  of  accomplishing  the  additional  task 
without  injury. 

McCarrison  summarized  his  evidence  as  to  the  intestinal  location  of 
the  disease  as  follows:  The  toxic  agent  is  introduced  into  the  system 
through  the  medium  of  water  or  food,  and  since  it  is  a  well-known  fact 
that  the  thyroid  secretion  possesses  to  a  high  degree  bactericidal  and 
antiseptic  powers,  therefore  a  powerful  antiseptic  which  exerts  its  action 
in  the  gut  cures  the  disease  just  as  the  lactic  acid  bacillus,  and  the  vac- 
cines, which  are  prepared  from  organisms  which  are  known  to  be  normal 
inhabitants  of  the  bowel,  cause  the  disappearance  of  goiter. 

In  the  microscopic  examination  of  feces  of  goiter  sufferers  McCar- 
rison very  constantly  encountered  amebae,  and  while  he  says  that  no 
definite  statement  as  to  the  pathogeny  of  these  amebae  can  be  made, 
their  possible  importance  is  obvious.  Since  1906  he  has  been  endeav- 
oring to  transmit  goiter  from  man  to  animals  by  infecting  the  water 
supply  of  the  latter  with  the  feces  of  goiter  sufferers.  Having  obtained 
only  negative  results  in  dogs,  goats  were  selected  for  the  experiment. 
These  animals  were  from  the  same  flock,  between  one  and  two  years  of 
age,  of  the  female  sex,  and  not  pregnant.  They  came  from  a  non-goiter- 
ous  locality,  and  upon  examination,  their  thyroids  showed  no  signs  of 
hypertrophy.  During  a  period  of  108  days  these  animals  drank  only 
water  which  had  been  highly  polluted  with  feces,  at  the  end  of  which 
time,  the  thyroid  was  distinctly  larger  than  normal,  and  on  microscopic 
examination  exhibited  an  increase  in  size  of  vesicles,  irregularity  and 
thinning  of  their  walls,  and  distention  of  vesicles  with  colloid.  Goats 
fed  on  cultures  of  bacteria  for  the  same  length  of  time  showed  a  tendency 
on  the  part  of  the  thyroid  gland  to  be  smaller  than  normal,  while  the 
histological  appearances  were  those  of  an  active  and  very  pronounced 
hyperplasia. 


THEORIES  REGARDING  THE  ETIOLOGY  OF  GOITER  275 

This  diminution  in  size  has  been  noted  by  other  experimenters: 
Edmonds  found  in  a  partially  thyroidectomized  dog  that  the  remaining 
lobe,  although  macroscopically  smaller  than  normal,  showed  marked 
hyperplasia  under  microscopic  examination.  Farrant  also  concluded 
that  the  earliest  stages  of  hyperplasia  are  associated  with  diminution 
in  size  rather  than  an  increase. 

General  Conclusions. — I.  We  can  accept  as  an  established  fact  that  the 
goiter  causative  factor,  whatever  its  nature  may  be,  is  most  frequentlv 
conveyed  to  the  organism  through  drinking  water. 

II.  The  activity  of  the  goiter  causative  factor  is  of  an  evanescent 
and  fleeting  character.  It  is  destroyed  by  ebullition,  materially  dimin- 
ished by  filtration,  and  loses  its  goitengenous  power  when  exposed  for 
a  certain  time  to  the  air.  The  goiterigenous  power  of  water  allowed  to 
stand  in  reservoirs  is  far  more  marked  at  the  bottom  of  the  body  of 
water  than  at  the  top. 

III.  Heredity  is  an  important  factor  in  the  etiology  of  goiter. 

IV.  Theories  seeking  to  establish  a  correlation  between  certain  geo- 
logical formations  and  endemic  goiter  are  no  longer  dependable.  The 
same  is  true  for  the  theories  claiming  that  lime,  magnesium,  metallif- 
erous rocks,  chalk,  etc.,  must  be  regarded  as  causative  factors.  Goiter 
is  found  in  every  latitude,  and  in  low  as  well  as  in  high  altitudes. 

V.  Although  very  clever,  Repin's  or  the  Plutonian  Theory  is  purely 
hypothetical. 

VI.  There  is  no  causal  relation  between  radio-activity  of  certain  waters 
and  goiter. 

VII.  There  seems  to  be  enough  evidence  to  show  that  goiter  is  not 
propagated  by  contact. 

VIII.  So  far  the  weight  of  evidence  seems  to  be  in  favor  of  the 
"infection  theory."  Chagas'  thyroiditis  is  a  very  strong  argument  in 
favor  of  that  theory.  Infection  takes  place  through  the  water  and  soil. 
\\  hat  is  the  nature  of  this  infection,  through  what  specific  agent  it  takes 
place,  is  not  known.  More  probably,  when  the  solution  is  obtained  the 
cause  will  be  found  to  be  within  conditions  which  are  quite  subject  to 
our  control,  as  has  been  the  case  for  malaria,  yellow  fever,  etc. 


CHAPTER   XVIII. 
MEDICAL  TREATMENT  OF  SIMPLE  GOITER. 

Treatment  of  goiter  may  be  prophylactic,  medicinal,  or  surgical. 

Prophylaxis. — The  best  prophylaxis  for  goiter  consists  in  avoiding  the 
regions  where  goiter  is  endemic,  and  this  is  especially  true  for  children  liv- 
ing in  endemic  regions,  and  whose  parents  have  goiter.  They  certainly 
would  be  much  better  off  if  they  could  spend  the  first  few  years  of  their 
lives  far  from  goiterigenous  influences,  as  it  is  during  this  early  period  of 
their  infancy  that  cretinism  and  other  forms  of  hypothyroidism  are  apt  to 
exert  their  greatest  ravages.  The  well-to-do  women  of  Valais  under- 
stood this  a  long  time  ago,  since  they  not  only  used  to  spend  all  the 
time  of  their  pregnancy  in  the  "Mayens"  of  the  Valesian  mountains, 
which  were  notoriously  non-goiterigenous,  but  they  also  left  their  little 
offspring  in  these  regions  for  the  first  year  or  two,  because  by  so  doing, 
they  learned  empirically  that  the  damages  caused  by  the  endemicity 
were  considerably  lessened. 

In  goiterous  women  living  in  endemic  regions  thyroid  opotherapy 
should  be  undertaken  from  the  beginning  of  the  pregnancy  and 
carried  all  the  way  through.  It  may  not  only  benefit  the  mother 
by  preventing,  to  a  more  or  less  extent,  a  compensatory  hyper- 
trophy of  the  thyroid  due  to  pregnancy,  but  it  may  also  pre- 
vent the  little  child  from  having  a  congenital  goiter.  Goiterous 
women  living  in  endemic  regions  while  nursing  their  babies  should  fol- 
low during  all  that  time  medical  treatment  with  thyroid  extract.  In 
short,  the  same  method  of  prophylactic  measures  employed  to  prevent 
the  child  from  the  consequences  of  a  syphilitic  infection  of  the  father 
or  mother,  or  of  both  together,  should  be  applied  to  protect  the  little 
child  from  the  consequences  of  endemic  parental  goiter. 

If  adults  who  are  slightly  affected  with  endemic  goiter  go  and  live 
in  regions  where  endemic  goiter  is  unknown,  the  chances  are  great  that 
the  goiter  contracted  in  the  endemic  region  will  disappear.  This  has 
been  observed  quite  a  number  of  times  with  young  soldiers  changing 
barracks,  etc. 

Hygienic  conditions  seem  to  be  of  importance  in  the  prevention  of 
goiter.  It  has  been  shown  time  and  time  again  that  the  introduction 
and  advance  of  hygienic  conditions  in  places  where  goiter  was  extremely 
frequent,  as  the  improvement  in  houses,  food,  clothing,  and  in  personal 


MEDICAL   TREATMENT  OF  GOITER  277 

cleanliness,  in  drainage,  and  through  the  construction  of  roads,  have 
materially  diminished  the  number  of  goiters  or  have  entirely  eliminated 
them.  More  than  once  it  has  been  shown  that  entire  villages  or  small 
portions  of  regions  have  been  delivered  from  endemic  goiter  by  provid- 
ing a  new  source  of  water  supply,  or  by  constructing  water-tight  canali- 
zations and  large  reservoirs  where  water  may  be  plentifully  stored  and 
aerated. 

\\  hen  one  must  live  in  a  country  where  goiter  is  endemic,  the  best 
prophylaxis  for  it  is  boiling  the  water.  Filtering  the  water  is  not  so  effec- 
tive. It  has  been  shown  experimentally  that  filtering  the  water  through 
a  Cumberland  or  Berkefeld  filter,  for  instance,  does  not  entirely  protect 
against  goiter. 

MEDICAL    TREATMENT   OF   GOITER. 

A  surgeon  might  think  that  because  all  the  goiters  which  come  under 
his  observation  have  more  or  less  failed  to  respond  to  medical  treat- 
ment that  the  latter  is  of  no  avail.  This  would  be  erroneous.  As  a 
matter  of  fact,  a  large  proportion  of  goiters  which  are  cured  either 
spontaneously  or  by  medical  means  never  come  under  the  observation 
of  the  surgeon.  They  have  recovered  under  dietetic,  hygienic,  and  medi- 
cal treatment.  Medical  treatment  has  its  own  field,  and  no  conscien- 
tious surgeon  will  deny  that  there  is  a  certain  category  of  goiters  which 
are  purely  medical.  On  the  other  hand,  no  learned  and  honest  internist 
will  refuse  to  admit  that  there  is  a  class  of  goiters  which  are  purely 
surgical.  It  would  be  indeed  just  as  sad  and  blamable  for  a  surgeon  to 
advocate  an  operation  for  even'  thyroid  hyperplasia  seen,  for  instance, 
at  the  time  of  puberty,  or  during  pregnane)*,  as  it  would  be  for  an 
internist  to  treat  systematically  with  thyroid  extract,  iodin,  or  any  other 
medicament,  cystic  or  nodular  colloid  goiters.  In  everything  there  is 
a  "juste  milieu,"  a  just  medium.  Each  form  of  treatment  has  its  own 
indications  and  contra-indications.  There  is  no  more  sufficient  reason 
to  discard  medical  treatment  because  it  has  failed  in  a  certain  number 
of  cases,  than  there  is  to  discard  surgical  treatment  because  a  certain 
percentage  of  patients  so  treated  died  from  operation. 

Indications  for  Medical  Treatment. — Medical  treatment  is  especially 
successful  in  the  parenchymatous  forms  of  thyroid  hyperplasia,  seen  at 
the  time  of  puberty,  pregnancy,  and  at  the  time  of  menopause.  A  diffuse 
colloid  degeneration,  when  the  latter  is  not  too  far  advanced,  may,  too, 
be  influenced  by  thyroid  opotherapy  or  by  iodin  treatment.  As  a  rule 
with  nodular  colloid  or  cystic  goiter  there  is  a  concomitant,  paren- 
chymatous hypertrophy  which  must  be  regarded  as  an  attempt  by 
Nature  to  compensate  the  lost  function  of  the  degenerated  portions  ol 


278  MEDICAL  TREATMENT  OF  SIMPLE  GOITER 

the  thyroid  gland.  Such  parenchymatous  hypertrophy  responds  readily 
to  iodin  treatment  and  soon  diminishes  in  volume,  hence  the  belief 
of  the  public  and  the  error  made  by  many  physicians  that  the  colloid 
or  cystic  nodule  has  become  smaller,  when  in  fact  it  has  retained  the 
same  size,  but  the  gland  in  toto  appears  to  be  smaller  because  the  paren- 
chymatous hypertrophy  alone  has  subsided.  In  conclusion  we  may 
say  that  medical  treatment  is  successful  in  all  forms  of  parenchymatous 
hyperplasia  which  seem  to  be  of  compensatory  nature,  as  at  the  time  of 
puberty,  pregnancy,  menopause,  etc.,  and  which  so  strikingly  resemble 
the  compensatory  hypertrophy  seen  by  Halstead  after  the  removal  of 
a  portion  of  the  gland.  These  compensatory  hyperplasias  and  others, 
as  those  accompanying  nodular  goiters,  may  be  prevented  by  thyroid 
feeding,  or  iodin  medication,  and  may  be  cured,  too,  by  the  same  treat- 
ment. If,  however,  the  hyperplasia  has  gone  too  far,  the  parenchyma 
does  not  return  any  more  to  its  previous  normal  condition,  and  hence 
induces  the  formation  of  a  permanent  goiter. 

But  medical  treatment  has  its  own  limitations.  In  1895  Bruns 
("Beobachtungen  und  Untersuchungen  iiber  die  Schildrusen-Behandlung 
des  Kropfes,"  Beitrdge  zur  klin.  Chir.,  Bd.  xvi,  Heft  2)  reported  a  series  of 
300  goiters  treated  by  thyroid  extract  with  the  following  results: 

Complete  cure 8  per  cent. 

Marked  improvement 36         " 

Slight  improvement 36         " 

No  improvement 20         " 

Three-fourths  of  the  cases  that  improved  relapsed. 

Contra-indications  to  Medical  Treatment.— 1.  Medical  treatment 
is  useless  in  colloid,  cystic,  fibrous,  calcareous,  and  nodular  goiters.  It 
may,  however,  be  valuable  before  operation,  by  reducing  to  a  minimum 
the  concomitant  compensatory  hyperplasia  which  is  often  observed. 
This  does  not  only  facilitate  the  surgical  act,  but  also  prevents  the 
surgeon  from  removing,  with  the  nodular  goiter,  a  too  great  amount  of 
glandular  hyperplasia  which  would  expose  the  patient  to  symptoms  of 
hypothyroidism. 

2.  When  diffuse,  colloid  goiters  have  resisted  an  intelligent  medical 
treatment  for  two  or  three  months,  there  is  no  need  to  insist  any  longer. 
Such  cases  must  be  turned  over  to  the  surgeon. 

3.  Every  goiter  causing  pressure  symptoms,  especially  every  intra- 
thoracic goiter,  and  since  there  is  here  little  to  be  expected  from  medical 
treatment,  must  be  treated  by  operation.  The  same  is  true  of  those 
goiters  which  produce  cardiac  symptoms. 


MEDICAL   TREAT M EXT  OF  GOITER  279 

4.  Medical  treatment  is  dangerous  in  those  forms  of  goiter  which 
grow  rapidly;  which  become  sensitive  to  pressure;  which  cause  referred 
pains,  which,  in  short,  are  suspicious  of  malignancy.  In  such  cases, 
every  day  devoted  to  medical  treatment  means  that  much  chance  lost 
for  a  radical  cure. 

5.  Medical  treatment  is  useless  in  strumitis.  In  these  cases  the 
ideal  treatment  would  be  to  remove  the  affected  lobe  en  bloc  before 
peristrumitis  has  gone  too  far,  and  before  abscess  formation  and 
perforations  have  taken  place. 

Medicaments. — The  medical  treatment  of  goiter  is  as  old  as  the  his- 
tory of  goiter  itself.  The  disease  was  one  of  those  to  which  the  most 
fantastic  remedies  of  the  Middle  Ages  were  applied.  Indeed  it  was 
among  the  maladies  supposedly  healed  by  the  King's  touch.  The 
Kings  of  England,  and  the  crowned  and  anointed  Kings  of  France  were 
thought  to  possess  the  power  of  curing  certain  diseases  bv  touching 
the  patient  and  by  making  the  sign  of  the  cross  above  them  while 
pronouncing  these  words,  "Le  Roy  te  touche,  Dieu  te  guerisse." 

The  touch  of  a  dead  hand  was  another  popular  remedy  for  goiter, 
and  is  mentioned  as  such  by  Pliny.  It  was  thought  that  the  goiter  would 
disappear  as  soon  as  the  dead  body  with  which  it  had  been  brought  in 
contact  became  disintegrated  by  decomposition  and  decay.  Peculiarly 
efficacious  was  thought  to  be  the  touch  of  a  body  killed  bv  drowning 
or  execution.  A  still  more  curious  treatment  consisted  in  enclosing  a 
small  living  animal,  such  as  a  lizard  or  toad,  in  a  sack  and  binding  this 
upon  the  goiter  where  the  animal  was  allowed  to  die  and  thus  was 
thought  to  carry  off  the  disease  in  expiring.  Amulets  and  loathsome 
remedies  such  as  excrements,  etc.,  were  among  the  recognized  methods 
of  treatment. 

\  ery  old  and  general  is  the  belief  in  the  influence  of  the  different 
phases  of  the  moon  upon  goiter,  and  it  is  still  customary  in  the  Enns 
valley  for  the  goiter  patient  to  go  out  at  night  and  gaze  fixedly  at  the 
moon  while  holding  his  goiter  with  his  right  hand  and  repeating  these 
words: 

"Was  ich  sehe  nehme  zu  (Let  what  I  am  looking  at,  grow  I. 
Was  ich  fasse,  nehme  ab  (Let  what  I  grasp,  get  smaller). 
In  namen  des  Vaters,  des  Sohnes,  und  des  Heiligen  Geistes.    Amen." 

Already  in  1200  Roger  von  Salerno  was  using  "toasted  sponges," 
toasted  egg-shells,  and  corals  as  treatment  for  goiter.  When  once  it 
became  known  that  the  success  of  such  treatment  was  due  to  the  10dm 
content  of  these  medicaments,  it  became  logical,  of  course,  to  use  iodin 
itself  in  goiter  therapy. 

Iodin  in  Treatment  of  Goiter.  -It  was  the  Swiss  physician,  Coindet,  in 
1829,  who  was  the  first  to  use  iodin  as  a  therapeutic  measure  againsl 


280  MEDICAL   TREATMENT  OF  SIMPLE  GOITER 

goiter.  Since  then  it  has  become  of  daily  use,  and  in  fact  it  is  still 
today  the  only  specific  treatment  we  have  for  simple  goiter.  We  may 
say  that  medical  treatment  of  simple  goiter  is  contained  in  this  one 
word:  iodin.  Thyroid  opotherapy  has  proved  to  be  a  valuable  asset 
in  therapeutic  treatment  of  goiter,  but  its  success  seems  to  be  in 
direct  proportion  to  the  10dm  content  of  the  thyroid  extract. 

That  iodin  influences  goiter  is  a  fact  which  is  empirically  very  well 
established.  But  why  does  it,  and  how?  The  answer  to  this  question 
presupposes  a  complete  knowledge  of  the  physiology  and  chemism  of  the 
thyroid  gland.  Unfortunately  these  two  branches  of  medicine  are  still 
in  their  infancy.  I  have  read  theories,  I  have  tried  to  elaborate  some, 
none  were  or  are  satisfactory.  Consequently,  I  had  better  leave  the 
question  open.  Two  facts,  however,  seem  to  be  probable:  (i)  Iodin 
activates  the  functional  activity  of  the  epithelium,  and  accelerates  the 
liquefaction  of  the  colloid.      (2)  It  acts  as  an  antiseptic. 

Up  to  date  iodin  has  been  used  mostly  under  the  form  of  iodide  of 
potassium  or  sodium.  It  may  be  used  externally  or  internally.  For 
internal  use  the  saturated  solution  of  KI  is  best  suited.  Ten  to  fifteen 
drops  a  day  will  be  amply  sufficient. 

Externally  iodin  may  be  applied,  before  going  to  bed  at  night,  on 
the  cervical  region  under  the  form  of  an  ointment  which  is  gently  rubbed 
in  for  about  5  to  10  minutes,  and  the  neck  then  covered  with  a  flannel 
cloth.  I  advise  rubbing  the  medicament  over  the  cervical  region  purely 
from  a  psychological  stand-point.  Patients  are  more  apt  to  follow  the 
treatment  faithfully  if  they  think  that  the  medicine  prescribed  attacks 
the  goiter  directly.  In  fact  it  does  not  matter  what  part  of  the  body  is 
rubbed,  provided  that  iodin  is  absorbed  in  some  way  or  another.  In 
order  to  be  more  active,  this  ointment  must  contain  free  iodin;  therefore 
it  is  better  to  wait  until  natural  oxydative  processes  have  set  free  some 
iodin  by  decomposing  KI;  this  condition  is  obtained  when  the  ointment 
has  taken  a  yellow  color.  The  same  results  may  be  obtained  by  adding 
at  the  start  a  few  drops  of  tincture  of  iodin. 

1$ — .Kal.  iodat 10  grams 

Aq.  dest 10 

Lanolin 30       " 

Vaseline 70       " 

Tinct.  of  iodin xxx  drops 

M.D.S. — For  friction  at  night. 

Iodin  under  the  form  of  syrup  of  iodide  of  iron  may  give,  too,  good 
results  and  especially  as  a  prophylactic  measure  during  pregnancy, 
puberty,  etc. 

Painting  with  iodin  should  be  entirely  discarded,  as  it  blisters  the 
skin  and   soon   prevents  the  continuation  of  the   treatment.      Further- 


MEDICAL   TREATMENT  OF  GOITER  281 

more,  it  is  a  dirt}'  therapeutic  measure  which  has  no  special  advantage, 
and  which  can  easily  be  replaced  by  any  one  of  the  above-described 
forms  and  methods. 

When  thyroid  opotherapy  is  adopted  for  treatment,  small  doses 
should  be  used,  from  o.i  to  0.2  of  dried  substance  or  one  tablet  of  5 
grains  every  day.  It  is  far  better  to  administer  small  doses  for  a  longer 
period  than  large  doses  over  a  short  period.  With  such  method,  one  is 
less  apt  to  have  symptoms  of  intoxication,  and  furthermore,  the  treat- 
ment may  be  protracted  long  enough  until  the  goiter  has  entirelv  sub- 
sided. The  chances  for  permanent  results  are  better,  too.  It  should, 
however,  always  be  borne  in  mind  that  many  of  these  thyroid  prepara- 
tions are  perfectly  inert  on  account  of  some  faulty  process  in  their 
manufacture. 

Whatever  form  of  treatment  is  adopted,  the  physician  should  always 
remember  that  it  is  not  necessary  to  give  large  doses  of  any  one  of  the 
medicaments  used  for  goiter  treatment,  but  that  small  doses  are  just  as 
effective,  and  far  less  dangerous. 

The  researches  of  McCarrison  and  Messerli  are  too  interesting  to  be 
overlooked,  as  may  be  seen  in  the  chapter  on  Etiology  of  Endemic 
Goiter  and  Cretinism.  Accordingly,  intestinal  disinfection  should  be 
undertaken  in  conjunction  with  the  iodin  medication.  Mild  laxatives 
and  intestinal  disinfectants  should  be  prescribed  daily  during  the  whole 
period  of  treatment.  Thymol,  salol,  creosote,  etc.,  may  be  used.  I 
give  preference  to  salol  and  creosote  since  thymol,  when  an  acid-free 
diet  is  not  observed,  is  apt  to  cause  intense  burning  sensations  in  the 
stomach. 

The  relation  between  the  thyroid  and  all  the  other  organs  of  internal 
secretion  has  suggested  the  attempt  to  add  to  thyroid  opotherapy  the 
extracts  of  other  endocrine  glands.  The  results  so  far  have  not  been 
very  encouraging. 

X-rays  in  simple  goiter  have  not  given  satisfactory  results. 

Crotti's  Formula  for  Treatment  of  Non-toxic  Parenchymatous  Goiter.— Of 
late  I  have  been  using  the  following  formula  with  the  most  gratifying 
results: 

1$ — Sodium  Arsenate O.OOI  gram 

Potassium  Iodide 0.06 

Sodium  Phosphate 0.2 

I  hyroprotein        ...  0.02       " 

Salol 0.2 

( !hocolate  coated.) 

I).  S.     One  tablet  three  times  a  day  <m  empty  stomach. 

These  compressed  tablets  are  easy  to  take,  are  well  tolerated,  and 

usually  do  not  cause  symptoms  of  intoxication.      I  shall  be  glad   to  have 


2S2  MEDICAL  TREATMENT  OF  SIMPLE  GOITER 

anyone  who  gives  them  a  trial,  report  to  me  as  to  their  efficacy  and 
tolerance.  They  were  prepared  for  me  by  Parke,  Davis  &  Co.,  Detroit, 
Michigan.  I  have  no  objection  to  having  any  other  reputable  firm  prepare 
them.     I  call  them  simple  goiter  tablets.     It  is  not  a  patent  medicine. 

Whatever  form  of  medical  treatment  is  employed,  patient  and 
physician  must  be  prepared  to  see  relapses  of  the  goiter  quite  frequently. 

Dangers  of  Iodin  Medication. — Iodin  given  during  too  long  a  period 
of  time,  or  in  too  large  doses,  not  only  produces  the  classical  symptoms 
of  intolerance,  such  as  salivation,  watering  of  the  eyes,  and  congestion 
of  the  nasopharyngeal  mucous  membrane,  but  may  also  give  rise  to  the 
worst  thyrotoxic  symptoms  so  similar  to  those  seen  in  Basedow's  dis- 
ease that  they  have  been  called  by  Breuer,  "Iodin-Basedow."  Every 
surgeon  who  has  had  some  experience  in  goiter  surgery  has  seen,  I  am 
sure,  more  than  once  these  artificially  produced  cases  of  Graves'  dis- 
ease caused  simply  by  an  untimely,  exaggerated,  and  unintelligent 
treatment  with  iodin  or  its  compounds.  It  should  be  borne  in  mind 
that  iodin  treatment  for  goiter  does  not  need  to  be  prolonged  over  a 
very  long  period  of  time,  nor  does  it  need  to  be  intense,  in  order  to  be 
successful.  When  iodin  is  going  to  be  active,  it  shows  its  efficacy  very 
soon,  say,  after  a  period  of  two  or  three  weeks.  Consequently,  if  after 
a  treatment  of  two  or  three  months  with  small  doses  of  the  medicament, 
no,  or  very  little,  improvement  has  been  obtained,  the  medical  treat- 
ment should  be  stopped.  When  successful,  the  treatment  for  safety's 
sake  ought  to  be  interrupted  for  small  periods  of  rest  of  a  few  weeks  in 
order  to  avoid  symptoms  of  intoxication.  We  must  not  forget  that  there 
are  patients  who  react  so  intensely  to  small  amounts  of  iodin  that  not 
only  do  the  worst  symptoms  of  intoxication  follow,  but  the  goiter  itself, 
instead  of  getting  smaller,  increases  in  size.  There  are  people,  too, 
who  are  so  extremely  sensitive  to  iodin  that  a  simple  sojourn  at  the 
seashore,  or  the  use  of  certain  mineral  waters,  is  sufficient  to  cause  in 
them  marked  thyrotoxic  symptoms.  It  should  be  always  remembered 
that  there  are  goiters  which  are  latent  Basedozv  goiters,  in  which  iodin 
medication  is  apt  to  start  the  "unhinging  of  the  thyroid  mechanism," 
whose  consequences  no  one  can  foresee. 

There  is,  too,  a  class  of  patients  to  whom  the  iodin  treatment  must 
be  administered  with  great  care  and  under  the  constant  supervision  of 
a  physician.  They  are  patients  whose  goiters  are  complicated  with 
thyrotoxicosis,  with  a  chronically  inflamed  respiratory  apparatus,  or 
goiters  which  are  manifestly  functionally  insufficient.  Medical  treat- 
ment must  be,  too,  carefully  watched  in  patients  with  obesity,  myocar- 
ditis, diabetes,  and  nephritis. 


TREATMENT  OF  THYROID  INSUFFICIENCY  283 

TREATMENT  OF  THYROID  INSUFFICIENCY. 

The  treatment  of  thvroid  insufficiency  may  be  medical  or  surgical. 
The  first  method  includes  thyroid  opotherapy;   the  second,  grafting. 

Thyroid  Opotherapy. — Modern  opotherapy  took  birth  the  day 
Brown-Sequard  announced  his  theories  on  internal  secretion.  Already 
in  1869  that  great  physiologist  had  expressed  the  opinion  that  all  the 
glands  of  the  organism,  with  or  without  excretory  canals,  throw  into 
the  blood  active  and  useful  principles  whose  absence  is  detrimental  to 
the  organism.     From  that  day  the  basis  of  scientific  opotherapy  was  laid. 

Theoretically,  opotherapy  aims  to  give  back  to  the  organism  the 
natural  products  of  the  sec'retion  of  a  gland,  whose  function  is  absent 
or  has  become  insufficient  or  perverted.  In  order  to  be  efficacious, 
these  products  must  consequently  be  qualitatively  and  quantitatively 
similar  to  the  ones  secreted  normally.  Practically,  these  conditions  have 
not  vet  been  obtained.  Inasmuch  as  our  organism  is  the  laboratory 
where  the  most  complicated,  most  varied,  and  the  most  delicate  chemi- 
cal metabolistic  reactions  take  place,  it  follows  that  only  an  accurate 
knowledge  of  these  processes  will  enable  us  to  undertake  rational  and 
successful  therapeutic  measures.  This  problem  is  the  one  which  the 
study  of  internal  secretion  is  trying  to  solve.  The  farmer  of  today 
does  not  farm  his  land  in  the  same  blind,  empirical  fashion  as  formerly, 
but  requires  the  aid  of  the  chemical  laboratory  in  order  to  know  which  of 
the  chemical  constituents  of  the  soil  are  deficient,  and  which  are  not. 
He  then  treats  the  soil  accordingly.  In  the  same  way,  the  future  phy- 
sician will  be  able  to  call  into  play  the  numerous  isolated  products  of 
the  organs  of  internal  secretion  as  a  therapeutic  means  against  a  great 
many  pathological  conditions.  In  a  great  many  other  conditions  he 
will  use  chemical  products  which  will  prove  themselves  specific  for  these 
conditions,  as  has  "606,"  for  instance.  That  day  will  indeed  be  a  great 
day  which  will  see  the  future  physician,  instead  of  medicaments  whose 
action  is  problematical  and  at  any  rate  empirical,  employing  this  or 
that  compound  isolated  from  the  organs  of  internal  secretion,  or  some 
other  specific  product,  and  by  their  clever  use  restore  to  normal  a  dis- 
turbed metabolism.  Certainly,  the  future  of  internal  medicine  rests 
with  and  belongs  to   Biological  Chemistry. 

Dangers  of  Thyroid  Opotherapy. — In  fact,  from  the  beginning  of 
opotherapy,  it  has  been  observed  that  ill  animals  as  well  as  human  beings, 
thyroid  preparations  were  liable  to  cause  symptoms  of  intoxication. 
Bouchard  reported  headache,  irritability,  muscular  and  articular  pains. 
Murray  saw  after  the  administration  of  thyroid  preparations,  nausea, 
vomiting,  and  loss  of  consciousness.  Stabel  saw  a  patient,  who  had  been 
taking  a  thyroid  preparation  as  an  antifat,   become  delirious  and   die. 


284  MEDICAL   TREATMENT  OF  SIMPLE  GOITER 

Beclere  saw  similar  cases  and  considered  thyroid  products  as  cardiac 
poisons.  In  a  myxedematous  patient,  after  ingestion  of  92  gms.  of  thy- 
roid extract,  he  saw  a  marked  tachycardia,  tremor,  exophthalmos,  rise 
in  temperature,  and  increased  perspiration.  Symptoms  of  hyperthy- 
roidism have  been  frequently  noticed  in  connection  with  opotherapy. 
One  of  the  most  striking  cases  is  the  one  reported  by  Nothaft.  A  man 
in  good  health  in  order  to  reduce  obesity  undertook,  on  his  own  initia- 
tive, to  take  in  a  few  weeks  a  thousand  thyroid  tablets  of  5  grains  each. 
He  developed  a  typical  Basedow's  disease,  with  goiter,  exophthalmos, 
tremor,  increased  perspiration,  loss  of  flesh,  and  glycosuria.  The  medi- 
cation was  stopped  and  ten  months  after  the  patient  was  normal  again. 
Ferranni  reported  the  case  of  a  woman  who  took  thyroid  as  an  antifat 
cure,  6  to  8  tablets  a  day.  In  two  months  she  lost  8  kilos  in  weight  and 
complained  of  vertigo,  palpitation  and  insomnia.  Nevertheless,  she 
increased  the  quantity  of  thyroid  and  soon  began  to  get  nervous,  with 
pulse  150,  diarrhea,  and  constipation,  psychic  trouble  and  hallucina- 
tions. Boynet  reported  the  case  of  a  student  who,  during  eight  days, 
absorbed  six  to  eight  sheep  thyroids  daily.  He  soon  developed  a  swell- 
ing in  the  thyroid,  palpitations,  tremor,  and  an  extremely  advanced 
delirious  condition  which  subsided  only  after  the  medication  had  been 
entirely  discarded.  My  friend,  Gagnebin,  while  a  medical  student, 
submitted  himself  to  a  series  of  experiments  in  order  to  determine  the 
action  of  the  thyroid  on  the  normal  organism.  For  a  period  of  about 
two  weeks  he  absorbed  daily  one  lobe  of  the  thyroid  of  a  sheep.  At  the 
end  of  that  time  the  palpitations  had  become  violent,  while  fever  and 
abundant  sweating  were  present.  The  tremor  was  so  intense  that  he 
could  not  rise  nor  even  carry  his  food  to  his  mouth,  while  exophthalmos 
had  become  very  marked.  The  experiment  was  interrupted  and  all  the 
symptoms  gradually  disappeared.  This  toxicity  of  the  thyroid  prod- 
ucts has  been  confirmed  by  almost  everyone  who  has  resorted  to  thyroid 
opotherapy.  Gregor,  however,  seems  to  have  been  more  fortunate,  since 
he  never  met  with  toxic  accidents  in  cases  where  enormous  doses  were 
given,  such  as  45  grains  daily.  Usually,  however,  the  symptomatology 
was  found  to  be  very  much  the  same:  nervous  troubles,  characterized 
by  irritability,  insomnia,  vertigo,  and  headache;  digestive  troubles 
characterized  by  nausea,  vomiting,  diarrhea,  and  constipation;  cardio- 
vascular disturbances  characterized  by  tachycardia;  and  increased 
vascularization  of  the  thyroid  have  been  most  frequently  observed. 

Thyroid  intoxication  seems  to  center  its  effects  mostly  on  the  car- 
diac, nervous,  and  gastro-intestinal  systems.  Intoxication  is  due  to  the 
medicament  itself  just  as  it  is  seen  in  any  other  medicament  when  given 
in  too  large  or  too  prolonged  doses,  as,  for  example,  strychnine,  digi- 
talis, etc.     As  antifat,  thyroid  products  must  be  used  with  the  greatest 


TREATMENT  OF  THYROID  INSUFFICIENCY  2S5 

circumspection,  as  accidents  of  collapse  of  the  gravest  character  may 
occur.  Always  bear  in  mind  that  myocarditis  is  a  verv  frequent  corolla rv 
of  obesity. 

A  part  of  the  toxic  symptoms  following  thyroid  opotherapy  are  cer- 
tainly due  to  absorption  of  putrefied  products  which,  according  to  Lang 
and  Gregor,  occur  rapidly  in  the  thyroid.  They  may  be  partly  due  to 
choline,  to  methylamine,  to  products  of  autolysis,  and  to  the  presence 
of  toxic  lipoids.  This  is  corroborated  by  the  fact  that  ingestion  of  fresh 
thyroids  does  not  cause  such  toxic  symptoms.  Ghedini  claims  that  the 
same  toxic  symptoms  may  occur  with  the  pancreas,  thymus,  etc. 
Recently  Chamagne  has  found  that  thyroids  in  a  fresh  state  are  dan- 
gerous in  proportion  to  the  time  which  has  elapsed  since  their  removal; 
their  maximum  of  toxicity  is  to  be  found  between  the  fifth  and  sixth 
days.  If  the  thyroid  is  deprived  of  its  lipoids,  its  toxicity  is  consider- 
ably reduced. 

In  conclusion  we  may  say  that  the  thyroid's  toxicity  is  partly 
due  to  its  lipoids  which  are  very  labile,  and  to  the  products  of 
autolysis;  as  we  know,  the  toxicity  of  an  organ  is  in  proportion  to  the 
lability  of  its  lipoids.  Some  of  the  other  symptoms,  as  cutaneous  erup- 
tions, muscular  and  articular  pains,  must  be  referred  to  the  introduction 
into  the  organism  of  albuminoid  substances  of  animal  origin.  The 
remaining  group  of  symptoms,  however,  must  be  put  in  relation  with 
the  absorption  of  thyroid  extract.  They  constitute  what  we  call  thy- 
roidism  and  are  characterized  by  tachycardia,  headache,  vertigo,  mental 
excitation,  tremor,  dyspnea,  fever,  protrusion  of  the  eyes,  polyuria, 
glycosuria,  albuminuria,  polyphagia,  polydypsy,  loss  of  flesh,  etc. 
Thyroidism  of  a  moderate  degree  is  very  frequently  associated  with 
simple  goiter.  In  exophthalmic  goiter,  however,  it  may  acquire  great 
intensity. 

Ingestion  Method  of  Treatment. — After  a  long  period  of  experi- 
ments and  trials  it  is  now  universally  admitted  that  the  ingestion 
method  is  the  easiest  and  most  effective  treatment  in  thyroid 
insufficiency.  Intravenous  and  subcutaneous  injections  have  been 
entirely  discarded,  as  they  are  dangerous  and  do  not  offer  any 
advantage  over  the  ingestion  method.  Subcutaneous  injections  are 
not  only  dangerous  because  the  thyroid  products  are  not  sterile, 
but  also  because  they  determine  severe  symptoms  of  anaphylaxis. 
Rectal  feeding,  although  less  effective  than  feeding  by  mouth,  may  be 
employed  in  certain  conditions  when  it  is  necessary  to  spare  the  gastro- 
intestinal tract. 

Medical  treatment  should  be  started  with  small  closes  and  must  be 
pursued  with  extreme  care  and  vigilance.  In  this  way  symptoms  of 
intoxication,  such  as  vertigo,  sensation  of  heat,  headache,  etc.,  may  be 


2S6  MEDICAL   TREATMENT  OF  SIMPLE  GOITER 

spared  to  the  patient,  and  furthermore,  this  method  gives  him  time  to 
get  used  to  the  medication.  It  has  the  further  advantage  of  determining 
the  dose  which  is  necessary  for  each  given  case  to  be  therapeutically 
effective  and  not  to  be  harmful.  Even  in  myxedematous  patients  where 
a  priori  it  would  seem  logical  to  administer  large  doses  on  account  of 
the  suppressed  thyroid  function,  one  will  meet  with  disappointments 
and  failures  if  treatment  is  not  started  with  great  prudence  and  judg- 
ment. A  fortiori,  this  will  be  true  in  cases  of  partial  thyroid  insufficiency 
only.  In  such  conditions  we  have  no  means  of  knowing  how  much 
medication  will  have  to  be  given  in  order  to  obtain  good  therapeutic 
results,  hence  again  the  necessity  of  staVting  the  medication  with  small 
doses.  Furthermore,  we  should  always  bear  in  mind  the  possibility  of 
idiosyncrasy.  With  thyroid,  just  as  well  as  with  other  medications,  the 
most  severe  intoxications  have  been  known  to  follow  the  administration 
of  very  small  doses  of  thyroid  extract.  The  cause  of  these  side  actions 
is  not  known,  but  it  has  been  suggested  that  during  the  course  of  myx- 
edema, certain  substances  may  accumulate  in  the  organism  and  that 
these  substances  may  be  broken  down  by  the  thyroid  in  a  manner 
analogous  to  the  liberation  of  endotoxins  when  pathogenic  bacteria  are 
destroyed  in  large  numbers  in  the  body  during  the  course  of  treatment 
of  an  infectious  disease. 

In  the  treatment  of  thyroid  insufficiency,  what  are  the  glandular 
preparations  to  which  we  should  give  preference  ?  Theoretically,  the 
fresh  gland  taken  soon  after  the  animal  is  killed,  seems  to  be  the  ideal 
preparation,  yet,  such  is  not  the  case;  first,  because  there  is  great  diffi- 
culty in  obtaining  fresh  thyroids  just  when  they  are  needed;  second, 
because  fresh  thyroids  undergo  putrefaction  very  rapidly  and  conse- 
quently are  liable  to  cause  the  worst  symptoms  of  intoxication.  Further- 
more, since  the  therapeutic  activity  of  the  thyroid  varies  with  every 
animal,  and  in  the  same  kind  of  animal  varies  with  many  conditions, 
the  mixture  of  a  great  number  of  thyroid  glands  together  is  more  likely 
to  give  a  more  uniform  standard  of  activity.  These  requirements  are 
met  in  the  dried  substance,  providing  it  has  been  modified  in  the  least 
possible  degree,  and  has  not  undergone  putrefaction. 

The  powdered  desiccated  thyroid  is  a  yellowish,  amorphous,  odorless 
powder,  putrefaction  of  which  readily  betrays  itself  by  a  very  unpleasant 
odor.  When  the  latter  condition  is  present-  the  medicament  must  be 
discarded  at  once.  The  gland  is  official  as  "desiccated  thyroid  gland" 
U.  S.  P.  Powdered  desiccated  thyroid  is  best  given  under  the  form  of 
a  "cachet"  or  "wafer"  in  whatever  dose  thought  necessary.  We  must 
only  remember  that  the  powder  represents  about  five  times  its  weight 
of  fresh  gland,  consequently,  5  milligrams,  25  milligrams,  and  10  centi- 
grams represent  2§,  I2|,  and  50  centigrams  respectively  of  fresh  thy- 
roid.    To  insure  greater  uniformity  it  is  suggested  that  the  powder  be 


TREATMENT  OF  THYROID  INSUFFICIENCY  287 

required  to  yield  from  0.17  to  0.23  percent,  of  iodin  in  thyroid  combina- 
tion. It  is  best  to  start  with  one  dose  of  10  to  25  milligrams  of  powder 
even'  other  day  at  first,  then  every  day,  and  then  to  increase  the  dose 
to  what  is  deemed  necessary. 

It  is  to  the  credit  of  Burroughs-Wellcome  &  Co.,  Merck,  of  Darmstadt, 
Parke,  Davis  &  Co.,  Armour,  etc.,  to  have  put  on  the  market  a  thyroid 
extract,  prepared  with  the  greatest  care,  in  tabloid  form.  These  tab- 
loids contain  from  0.1  to  0.3  gr.  of  dried  substance.  It  is  well  to  begin 
the  treatment  with  one  tablet  in  order  to  try  out  the  susceptibility  of 
the  patient  to  the  medication  and  then  gradually  to  increase  the  dose 
until  the  most  effective  therapeutic  effect  is  obtained.  Children  may 
encounter  great  difficulty  in  swallowing  such  tablets,  and  in  that  case 
it  is  better  to  prescribe  the  thyroid  extract  in  liquid  form.  The  thyroid 
elixir  of  the  firm,  Allen  &  Hanbury,  of  London,  is  useful  in  such  conditions. 
One  teaspoonful  represents  0.1  centigram  of  thyroid. 

Whatever  form  of  thyroid  medication  is  adopted,  it  is  well  to  inter- 
rupt the  opotherapy  one  week  out  of  four.  When  the  results  are  as 
complete  as  can  be  expected,  a  dose  of  "maintenance"  should  be  kept  up, 
two  or  three  tablets  a  week,  for  instance,  otherwise  hypothyroidism  is 
bound  to  relapse. 

Arsenic  is  a  very  good  adjuvant  in  thyroid  opotherapy.  Hertoghe 
claims  that  the  thyroid  medication  is  very  much  more  active  and  better 
tolerated  if  the  blood  is  alkahmzed  with  bicarbonate  of  soda. 

At  first,  on  account  of  the  marked  degree  of  cachexia,  one  would  be 
tempted  to  join  to  the  thyroid  medication  a  fortifying  diet  such  as  eggs, 
wine,  or  meat,  thereby  hoping  to  ameliorate  more  rapidly  the  condition 
of  the  patient.  Such  views  are  erroneous.  We  have  seen,  in  dealing 
with  the  experimental  pathology  of  myxedema,  that  animals  fed  with 
a  meat  diet  show  much  earlier  and  more  severe  symptoms  than  do  those 
fed  with  a  vegetable  or  milk  diet.  It  is  common  knowledge  that  myx- 
edematous cachexia  in  children  appears,  or  becomes  rapidly  much  more 
marked,  at  the  weaning  time  and  especially  at  the  time  when  an  omniv- 
orous diet  is  substituted  for  the  milk  diet. 

We  have  seen,  too,  that  in  hypothyroidism  the  bodily  temperature 
is  invariably  lowered:  hence  the  indication  to  keep  such  patients  in 
warm  rooms,  to  avoid  cold  baths,  and  to  prescribe  warm  ones  instead, 
and  warm  fluids.  Such  adjuvants  will  materially  increase  the  effect  of 
thyroid  medication. 

Thyroid  opotherapy  must  be  used  in  every  form  of  thyroid  insuffi- 
ciency, surgical  and  congenital  athyroulisin,  spontaneous  infantile  and 
adult  hypothyroidism,  and  in  cretinism.  I  he  earlier  the  medication  is 
started,  the  more  brilliant  will  be  the  results.  The  medication  in  such 
conditions  is  specific  and  very  often    an    absolute    restitutio  ad  integrum 


288  MEDICAL  TREATMENT  OF  SIMPLE  GOITER 

takes  place.  It  is  remarkable  to  see  how  quickly  the  skin  loses  its  myx- 
edematous infiltration,  its  cyanotic  character,  and  becomes  warm;  and 
how  the  thick,  fatty  deposits  in  the  neck,  supraclavicular  spaces  and 
other  regions  of  the  body  gradually  disappear.  The  abdomen  becomes 
smaller.  Remarkable  changes  take  place  in  the  face  not  only  because 
the  myxedema  retrocedes,  but  also  because  the  intelligence  of  the  patient 
awakes,  and  its  apathetic  condition  disappears.  Menstruation  comes 
back  and  remains  regular,  the  nutritional  exchanges  tend  to  become 
normal;  the  movements  of  the  bowels  become  regular;  temperature  loses 
its  subnormal  character  and  oscillates  between  normal  limits.  In 
growing  children  the  changes  in  the  skeleton  are  remarkable.  After  a 
few  months  of  treatment  the  bones  grow  remarkably  and  ossification 
takes  place  rapidly  in  the  epiphyses  as  shown  by  the  ;c-rays.  It  is  not  infre- 
quent to  find  an  increase  of  8  to  10  cms.  in  the  course  of  five  or  six  months, 
even  if  the  patient  has  reached  the  advanced  age  of  twenty-five  or  thirty- 
five  years.  Unfortunately,  however,  the  amelioration  lasts  only  as  long 
as  the  treatment  is  kept  up. 

Opotherapy  in  surgical  athyroidism  or  cachexia  strumipriva  or 
thyreopriva  gives  wonderful  and  rapid  results.  If  accessory  thyroid 
glands  are  present,  they  have  time  during  thyroid  medication  to  undergo 
compensatory  hypertrophy,  so  that  after  awhile,  they  are  able  to  supply 
the  function  of  the  lost  thyroid.  If  cachexia  is  due  to  partial  thyroidec- 
tomy, since  thyroid  insufficiency  is  not  complete,  the  thyroid  medication 
will  at  once  restore  the  patient  to  his  normal  condition.  Here,  again,  it 
will  allow  the  remaining  portion  of  the  thy roid  to  undergo  a  secondary 
compensatory  hypertrophy  so  that  after  a  few  weeks  or  months,  the 
thyroid  medication  may  be  discarded  because  the  physiological  func- 
tion of  the  thyroid  has  again  become  sufficient. 

In  congenital  athyroidism  and  spontaneous  infantile  hypothyroidism 
thyroid  opotherapy  is  of  great  value.  The  earlier  the  opotherapy  is 
started,  the  more  successful  will  be  the  results.  When  nanism  and 
idiocy  have  acquired  a  marked  development,  the  cure  can  hardly  be 
expected  to  be  complete;  nevertheless,  under  treatment  the  changes 
are  marvellous.  There  is  a  marked  contrast  with  the  child  before  treat- 
ment and  the  same  one  after  a  period  of  medication.  Such  patients 
regain  their  energy,  enjoy  every  minute  of  the  day  a  constant  muscular 
activity  which  contrasts  markedly  with  their  previous  apathy  and 
marasmus.  Furthermore,  they  are  conscious  of  no  fatigue,  hence  the 
danger  of  acute  cardiac  dilatation  and  collapse,  and  hence  the  obliga- 
tion to  watch  these  patients  carefully.  V.  Robin  reports  the  sudden 
deaths  of  two  myxedematous  children  as  the  consequence  of  an  exag- 
gerated activity. 

According   to   Bang,   the   thyroid   principles   are   eliminated   mostly 


TREATMEXT  OF  THYROID  INSUFFICIENCY  289 

through  the  milk  secretion.  If  this  is  true,  it  might  be  advisable  to 
prolong  the  nursing  period  as  long  as  possible.  Spolbermi  claims  that  a 
child  nursed  by  a  goiterous  mother  may  develop  hypothyroidism,  and 
that  this  condition  can  be  relieved  at  once  if  a  new  nurse  is  provided, 
hence  the  indication  always  to  examine  the  mother  or  the  wet-nurse 
in  even'  case  of  suspected  thyroid  insufficiency  in  the  child. 

In  spontaneous  adult  hypothyroidism  the  results  of  opotherapy  are 
equally  good,  but  are  not  so  persistent  as  in  surgical  hypothyroidism, 
because  in  the  first  condition,  the  chances  for  having  accessorv  thyroid 
glands  are  remote.  If  they  had  been  present,  they  would  indeed  have 
undergone  a  secondary  compensatory  hypertrophy  during  the  time  the 
thyroid  was  becoming  insufficient,  and  would  then  amply  supply  the 
deficient  secretion  of  the  gland  and  thus  prevent  the  development  of 
hypothyroidism.  Consequently  if  present,  they  were  not  "Funktions 
fahig"  or  functionally  capable  enough  to  supply  the  thyroid  deficiency. 

Systematic  treatment  of  endemic  cretinism  is  more  of  a  social  prob- 
lem than  a  fight  against  each  individual  case.  It  is  not  only  a  humani- 
tarian question,  but  it  is  also  a  very  important  economical  problem.  If 
we  stop  to  think  that  in  Prance  alone  there  are  120,000  cretins,  that 
other  countries,  as  Switzerland,  Italy,  Austria,  etc.,  are  affected  in  about 
the  same  proportion,  if  not  more,  it  will  be  easily  understood  why  von 
Wagner,  and  Van  Jauregg,  of  \  ienna,  have  sought  to  have  Austria 
furnish  thyroid  medication  free  of  charge  to  its  inhabitants. 

Unfortunately,  in  endemic  cretinism  the  results  of  opotherapy  are 
not  as  good  as  in  other  forms  of  hypothyroidism.  Von  Wagner,  Magnus- 
Levi,  Weygandt,  Gauthier,  and  others  claim  to  have  had  good  results, 
but  others,  as  Bircher,  Scholz,  Kutschera,  etc.,  say  that  thyroid  opo- 
therapy has  no  influence  upon  cretinism.  At  any  rate  we  may  say  that 
the  treatment  of  a  well-established  case  of  cretinism  is  more  or  less 
hopeless.  Only  in  cases  where  an  early  diagnosis  is  made  before  the 
somatic  symptoms  have  reached  their  development,  and  provided,  that 
the  cretin  is  transferred  from  the  endemic  region  into  another  free  from 
goiter  and  cretinism,  and  submitted  to  an  intelligent  thyroid  treatment, 
can  we  hope  to  stop  the  development  of  the  disease.  In  that  way  the 
pathological  changes  in  the  skeleton  and  in  the  organs  of  sense  and  in 
the  intelligence  may  be  prevented.  In  fully  developed  endemic  cretin- 
ism, if  opotherapy  is  beneficial,  the  somatic  symptoms  show  improve- 
ment; the  intellectual  sphere,  however,  is  seldom  materially  benefited. 
Cretins  are  so  very  sensitive  to  thyroid  medication  that  they  may  show 
symptoms  of  thyroidism  characterized  by  nausea,  vomiting,  fever, 
tachycardia,  insomnia,  and  loss  of  flesh. 

The  best  prophylactic  measure  against  goiter  and  cretinism  is  to 
purify  the  drinking  water,  but  boiling  the  water  is  the  safest  prophylaxis. 

V) 


290  MEDICAL   TREATMENT  OF  SIMPLE  GOITER 

In  regions  where  goiter  is  endemic,  cistern  water  offers  a  great  deal  more 
security  than  the  ordinary  drinking  water.  In  regions  where  goiter  is 
endemic  people  have  remained  absolutely  free  from  goiter  and  cretinism 
by  building  cisterns  and  using  this  accumulated  rain  water  instead  of 
the  ordinary  water  of  the  vicinity. 

So  far  as  endemic  deaf  and  dumbness  is  concerned,  the  results  of 
thyroid  opotherapy  have  been  negative.  Every  effort  to  teach  these 
cretins,  as  is  done  in  deaf-and-dumb  asylums,  has  been  a  failure.  How- 
ever, Wagner  thinks  that  if  the  modern  methods  employed  in  the  asy- 
lums of  deaf  and  dumb  should  be  applied  to  these  cretins,  it  would  not 
be  impossible  to  obtain  some  results,  because  he  believes  that  the  disturb- 
ances are  peripheric,  being  caused  by  an  abnormal  development  of 
adenoids  which  interfere  with  the  Eustachean  tube  and  thus  cause  second- 
ary inflammation  in  the  hearing  apparatus.  Schwendt  and  Wagner 
found  pathological  changes  in  the  tympanic  membrane  and  anomalies 
in  the  hammer.  Wagner  found  a  chronic  middle-ear  catarrh  and  Alex- 
ander found  an  atrophy  of  Corn's  organ.  On  the  other  hand,  Kocher 
and  others  believe  that  these  disturbances  are  not  of  peripheric  but  are 
of  central  origin,  being  localized  in  the  cortical  centers,  and  are  of  the 
same  nature  as  auditive  and  sensorial  aphasia.  The  peripheric  hearing 
apparatus  is  able  to  transmit  the  impressions  but  the  central  nervous 
apparatus  is  unable  to  register  them. 

In  small  thyroid  insufficiency  or  fruste  forms  of  hypothyroidism  the 
results  obtained  by  opotherapy  have  surpassed  the  greatest  expecta- 
tions. As  we  have  seen,  Hertoghe,  Magnus-Levi,  Gauthier,  Thiberge, 
and  others  have  widened  this  field  and  recognize  that  hypothyroidism 
is  the  etiological  factor  of  many  pathological  conditions  which,  up  to 
then,  had  remained  a  blank  for  the  medical  profession. 

Polyglandular  Treatment. — On  account  of  the  functional  correlation 
which  exists  between  all  endocrine  glands,  and  on  account  of  the  influ- 
ences which  they  exert  one  upon  another,  it  is  easily  understood  that 
every  one  of  them  must  be  in  a  state  of  instable  equilibrium,  so  that 
disturbances  in  one  of  them  may  have  a  more  or  less  marked  repercus- 
sion upon  the  other  glands.  By  throwing  into  the  blood  compensatory 
or  antagonistic  products,  these  fellow-glands  may  be  able  to  hold  the 
physiological  balance  in  its  normal  limits,  but  in  other  conditions,  they 
may  not  succeed,  hence  the  disturbances  which  may  not  be  directly  in  a 
relation  with  thyroid  insufficiency,  but  which  are  related  to  it  only 
indirectly,  viz.,  by  disturbing  the  polyglandular  equilibrium.  Conse- 
quently, it  may  be  rational  in  certain  cases  to  add  to  the  thyroid  medi- 
cation the  opotherapy  of  the  glands  which  seem  physiologically  at 
fault.  Such  indications  will  be  the  result  only  of  a  careful  study  of  the 
symptoms  seen  in  the  patient  and  of  a  better  knowledge  of  the  function 
of  endocrine  glands. 


CHAPTER   XIX. 
THYROID  GRAFTING. 

Although  Schiff  had  shown  long  ago  that  transplanted  thyroid  was 
physiologically  active,  it  was  only  in  1883  that  Kocher  and  Bircher 
demonstrated  its  efficacy  as  a  therapeutic  measure,  and  since  then  it 
has  been  freely  used  by  many  other  surgeons.  Bircher  was  the  first  to 
transplant  the  human  thyroid  into  the  abdominal  wall  of  a  patient. 
The  results  were  good  but  only  temporary.  One  and  one-half  months 
after  transplantation  cachectic  symptoms  reappeared.  He  made  a 
second  grafting  wThose  results  were  not  permanent,  although  they  lasted 
longer  than  in  the  first  case.  Lubarsch  sought  to  transplant  thyroid 
into  the  kidneys.  Christiani  advocated  grafting  small  particles  of  thy- 
roid into  the  subcutaneous  tissues.  His  method  is  known  as  the  "graft- 
ing en  semis,"  and  consists  in  burying  small  particles  of  thyroid,  a  little 
larger  than  a  grain  of  rice,  into  the  subcutaneous  tissue.  Each  particle 
must  be  buried  separately  and  as  many  as  twenty-five  to  forty  of  these 
small  particles  may  be  placed  in  one  sitting.  Christiani  was  able  to 
demonstrate  histologically  that  twelve  years  after  grafting,  some  of 
these  small  glandular  particles  were  still  alive,  capable  of  function,  and 
that  the  myxedematous  symptoms  had  entirely  disappeared.  One  of 
his  cases  which  he  published  in  collaboration  with  Scharnn  is  of  great 
interest,  as  it  shows  that  this  method  can  be  successful.  A  young  girl, 
seventeen  years  old,  had  been  completely  thyroidectomized.  As  this 
patient  was  insufficiently  benefited  by  opotherapy,  Scharrin  and  Chris- 
tiani made  two  series  of  "grafting  en  semis."  The  patient  was  greatly 
benefited.  Two  years  after  she  became  pregnant  and  gave  birth  to  a 
normal  child.  Curiously  enough,  during  pregnane)'  several  of  the 
implanted  particles  showed  a  temporary  hypertrophy  similar  to  the  one 
seen  in  thyroids  of  pregnant  women.  One  of  Kocher's  patients  who  had 
been  grafted  with  thyroid  gland  in  the  abdominal  wall  two  years  previ- 
ously, developed  a  tumor  which  suppurated,  and  was  then  finally 
eliminated.     Symptoms  of  hypothyroidism  recurred  at  once. 

Payr  thought  that  the  organ  of  choice  for  the  transplantation  of  the 
thyroid  was  the  spleen.  The  results  in  one  of  Ins  cases  were  extremely 
brilliant.  In  a  six-year-old  child  affected  with  congenital  athyroidism, 
he  transplanted  into  the  spleen  of  the  child  a  portion  of  the  normal 
thyroid  belonging  to  the  mother.     Five  months  after,  the  little  patient 


292  THYROID  GRAFTING 

had  grown  12  cms.  Unfortunately,  notwithstanding  the  close  consan- 
guinity of  the  "donor"  with  the  "recipient,"  thus  enhancing  the  chances 
of  success  for  the  taking  of  the  graft,  the  results  did  not  remain  perma- 
nent since,  after  a  certain  period  of  time,  symptoms  of  thyroid  insuffi- 
ciency recurred.  Miiller  and  Moscowicz  transplanted  thyroids  into  the 
epiphysis  with  some  good  results.  Kocher  prefers  the  upper  part  of  the 
shaft  of  the  tibia,  von  Eiselsberg,  the  preperitoneal  fat,  as  the  place  of 
election  for  the  grafting  of  thyroid.  Whatever  method  of  grafting  is 
chosen,  too  often  the  results  are  only  temporary;  the  transplanted  part 
undergoes  a  gradual  resorption,  so  that  after  a  certain  time  the  trans- 
planted thyroid  develops  vascular  connection  with  the  neighboring 
tissues  and  may  then  become  permanent. 

The  solution  of  this  problem  was  thought  to  have  been  found  when 
Carrel  related  his  wonderful  experiments  on  vascular  anastomosis.  The 
promises  of  this  method  were  great,  yet,  deceptions  only  were  in  store. 
Although  Carrel,  Stich  and  Makkas,  Borst  and  Enderlein  were  able  in 
very  few  instances  to  report  successful  "autotransplantations,"  they 
invariably  failed  when  they  tried  "heterotransplantations."  In  a  series 
of  experiments  undertaken  in  that  line,  although  every  possible  aseptic 
precaution  was  taken  and  the  techmc  of  vascular  anastomosis  mas- 
tered, I  was  never  able  to  obtain  permanent  heterotransplantations. 
Invariably  six  to  twelve  weeks  after  every  trace  of  the  transplanted  thy- 
roid had  more  or  less  entirely  disappeared;  all  that  remained  was  a 
small  mass  of  connective  tissue. 

In  conclusion  we  may  say  that  up  to  date  the  permanency  of  the 
results  of  thyroid  grafting  are  in  the  great  majority  of  cases  doubtful; 
their  immediate  results,  however,  are  brilliant  and  are  due  to  the  resorp- 
tion of  the  grafted  thyroid  tissue  instead  of  its  function. 

So  far  the  usual  methods  of  grafting  are:  the  subcutaneous  method 
of  Christiani,  or  "grafting  en  semis"  described  above,  and  the  one  advo- 
cated by  Kocher,  namely,  transplantation  in  the  spongiosa  tibicz. 
Instead  of  making  the  graft  subcutaneous  I  prefer  to  implant  the  thy- 
roid in  the  preperitoneal  space.  However,  it  is  best  to  combine  all  these 
methods  whenever  any  grafting  is  undertaken.  Furthermore,  the  grafts 
must  be  numerous,  as  many  are  bound  not  to  "take." 

Transplantation  in  the  spongiosa  tibiae  (Fig.  58)  has  given  in  the 
hands  of  Kocher  excellent  results.  This  region  being  near  the  epiphyseal 
line  is  very  vascular;  the  lacunes  are  large  and  thin,  and  a  hole  large 
enough  to  receive  the  graft  can  easily  be  made.  The  graft  lies  there 
comfortably  without  undue  pressure;  however,  the  graft  must  be  of  the 
same  size  as  the  hole,  so  that  no  dead  space  exists  between  the  wall  of  the 
hole  and  the  graft.  This  is  essential  for  success.  Hemorrhage  must  be 
entirely    stopped    by    packing   before   grafting.     This   is   of  the   utmost 


THYROID  GRAFT  I XG 


293 


importance,  too,  because  if  hemorrhage  occurs  the  graft  will  not  "take," 
or  at  least  will  be  greatly  endangered,  because  hemorrhage  infiltrates 
the  graft,  becomes  organized  and  finally  gives  rise  to  connective  tissue 
which  will  ultimately  destroy  the  glandular  graft. 

The  gland  to  be  grafted  must  be  well  nourished  and  as  active  as 
possible.  Kocher  recommends  the  use  of  thyrotoxic  gland  whenever 
possible.  If  this  is  not  possible  he  advised  treating  the  "donor"  some 
time   beforehand   with   10dm   in   order   to   stimulate   the   thyroid.      The 


Fig.  58. — Figure  showing  cavity  in   the  spongiosa   tibize  for  grafting  of  the   thyroid. 


graft  is  taken  during  thyroidectomy  as  soon  as  it  is  removed  from  the 
"donor,"  and  must  be  at  once,  without  loss  of  time,  grafted  in  the 
little  cavity  prepared  in  the  tibia  1  Fig.  58)  of  the  "recipient."  The  rapid- 
ity of  this  transport  is  of  great  importance.  The  easiest  way  is  to  have 
the  two  patients  on  separate  tables  and  while  thyroidectomy  is  being 
performed  to  have  an  assistant  prepare  a  small  cavity  in  the  tibia  of  the 
"recipient."  The  size  of  the  graft  must  not  exceed  twice  the  sizeofa 
cherry    stone.       Every    trace    of   glandular    capsule    must    be    carefully 


294  THYROID  GRAFTING 

removed  because  this  capsule  prevents  the  neoformation  of  vessels 
between  the  graft  and  the  neighboring  tissues.  After  the  graft  has 
been  carefully  placed  in  the  cavity,  the  periosteum  and  the  skin  are 
carefully  sewed  up  separately.  In  order  to  obtain  as  complete  a  vacuum 
as  possible  it  is  safer  before  closing  up  the  periosteum  to  create  a  small 
vent  in  order  to  allow  air  to  escape. 

It  is  highly  probable  that  most  of  the  unsuccessful  graftings  must 
be  attributed  to  the  poor  general  condition  of  the  tissues  receiving  the 
graft,  especially  the  subcutaneous  ones.  How  could  it  be  otherwise  ? 
A  glandular  graft  transplanted  in  a  "milieu"  or  medium  soaked  with 
myxedema  and  poorly  vascularized  is  bound  to  be  not  "viable."  Hence, 
in  my  judgment,  an  indication  of  great  importance:  before  grafting  the 
patient  should  be  submitted  to  an  intense  thyroid  opotherapy  in  order 
to  "demyxedematize"  him  as  much  as  possible.  When  that  is  done 
grafting  may  be  attempted,  and  opotherapy  kept  up  until  the  graft  has 
presumably  "taken." 

However,  despite  every  precaution,  grafting  of  the  thyroid  will  still 
remain  uncertain  because  the  graft  is  transplanted  into  new  surroundings 
endowed  with  entirely  different  physiological  properties.  The  solution 
of  the  problem  lies  in  the  discovery  of  the  means  capable  of  modifying 
the  serum  of  the  donor  or  recipient,  or  both  together,  so  as  to  render 
them  closely  similar  chemically,  i.  e.,  isobiological. 


CHAPTER   XX. 
INDICATIONS   FOR  OPERATION  IN  SIMPLE  GOITER. 

We  may  say  that  thyroidectomy  undertaken  under  correct  indica- 
tions and  performed  with  good  technic  is  practically  without  danger 
and  must  be  undertaken: 

i.   In  every  case  where  medical  treatment  has  failed. 

2.  In  all  colloid,  fibrous,  cystic  goiters  (Figs.  59-62). 

3.  In  all  diffuse  colloid  goiters  which  have  resisted  medical  treatment. 

4.  In  all  goiters  which  are  partially  or  totally  intrathoracic. 

5.  In  all  goiters  causing  pressure  symptoms  on  the  trachea,  esopha- 
gus, on  the  inferior  laryngeal  and  sympathetic  nerves,  and  on  the  arterial 
and  venous  trunks. 

6.  In  all  goiters  having  a  tendency  to  produce  a  goiter-heart,  be  it 
mechanical  or  thyrotoxic. 

7.  All  goiters  causing  unsightly  deformities. 

8.  In  all  vascular  goiters,  thyrotoxic  or  not. 

9.  In  all  goiters  secondarily  complicated  with  symptoms  of  hyperthy- 
roidism. 

10.  In  all  goiters  which  after  a  period  of  latency,  especially  at  the 
time  of  menopause,  suddenly  begin  to  grow,  show  changes  in  consis- 
tency, lose  their  mobility,  and  cause  referred  pain.  These  goiters  are 
suspicious  of  malignancy  and  should  be  treated  by  operation  without 
delay,  regardless  of  the  patient's  age. 

11.  Operation  should  be  performed  in  all  cases  of  strumitis.  As  I 
have  said  before,  the  ideal  in  such  cases  is  to  remove  the  infected  lobe 
en  bloc  while  pus  is  still  well  encapsulated  and  before  peristrumitis 
has  taken  too  great  a  development.  If  this  is  no  longer  possible,  then 
the  abscess  should  be  lanced  and  drained. 

12.  As  a  general  principle,  I  would  say:  Do  not  wait  too  long  before- 
operating  any  one  of  the  cases  which  have  become  surgical.  The  ten- 
dency of  today's  surgery  is  to  be  not  only  curative,  but  also  to  be  pro- 
phylactic: we  aim  to  operate  before  complications  have  occurred.  In 
appendicitis,  we  do  not  wait  until  the  abdomen  is  full  of  pus,  we  do  not 
even  wait  until  the  appendix  has  ruptured.  At  the  first  symptom  we 
open  the  abdomen  and  remove  the  appendix.  In  so  doing  we  not  only 
cure  the  patient  of  his  present  attack,  but  also,  we  operate  before  tin- 
condition  has  had  time  to  become  dangerous:  we    thus  aelel  prophylaxis 


296 


LXDICATIOXS  FOR  OPERATION  IN  SIMPLE  GOITER 


to  cure.     In  our  gall-bladder  surgery,  we  do  not  wait  until  the  patient 
has  become  so  thoroughly  poisoned  by  jaundice  that  the  result  of  the 


Fig.  59. — Nodular  colloid  goiter. 


Fig.  60. — After  the  operation. 

operation  will  be  highly  problematical.     Nor  do  we  wait  until  a  gall- 
bladder empyema  has  perforated  into  the  abdominal  cavity  or  into  a 


IXDICATIOXS  FOR  OPERATIOX  IX  SIMPLE  GOITER  297 


Fig.  6i. — Nodular  colloid  goiter  involving  both  lobes  and  isthmus. 


Fig.  02.     I  en  daj  s  after  operai  ion. 


298  IXDICATIOXS  FOR  OPERATIOX  IX  SIMPLE  GOITER 

neighboring  organ  before  interfering  surgically.  At  the  first  symptoms 
we  intervene,  because  we  have  learned  at  the  cost  of  too  many  lives 
that  procrastination  too  often  causes  death,  or  failure  to  cure.  There, 
too,  the  cure  of  the  patient  is  no  longer  our  sole  object;  we  try  to  inter- 
fere before  the  situation  has  become  serious.  Here,  too,  we  add  prophy- 
laxis to  cure.  In  our  gynecological  work  we  do  not  delay  until  ovarian 
or  uterine  tumors  have  reached  a  monstrous  volume,  until  they  become 
malignant,  in  short,  until  they  have  endangered  the  patient's  life, 
before  we  advocate  surgical  treatment.  As  soon  as  these  organs  begin 
to  show  symptoms,  we  remove  them.  We  do  not  only  aim  to  cure  the 
patient  of  her  infirmity,  but  we  also  strive  to  operate  while  the  chances 
are  all  on  our  side,  hence  again  we  have  prophylaxis  and  cure  in  view. 
And  so  it  must  be  in  goiter  surgery.  Why  wait  until  the  goiter  has 
reached  an  unsightly  deformity,  caused  pressure  symptoms,  determined 
thyrotoxic  symptoms,  etc.,  before  operating  ?  Why  even  wait  until  it 
causes  many  symptoms  at  all  ?  As  long  as  the  goiter  has  become  surgical, 
the  earlier  the  operation  the  better  the  results  will  be  for  everybody 
concerned,  the  patient  and  the  surgeon.  As  we  remove  any  tumor  of 
the  breast  for  fear  of  malignancy,  no  matter  if  that  tumor  gives  symp- 
toms or  not,  so  I  believe  we  should  remove  any  surgical  goiter  for  fear  of 
mechanical  symptoms,  of  thyrotoxic  symptoms,  and  for  fear  of  malig- 
nancy. Here,  too,  prophylaxis  goes  hand  in  hand  with  cure.  Of  course 
I  am  speaking  of  the  surgical  cases  only:  whenever  there  is  a  chance  for 
medical  treatment  it  must  be  employed  judiciously.  One  should  use 
his  best  judgment,  and  should  not  allow  his  medical  conscience  to  devi- 
ate in  the  slightest  degree  from  the  right  path.  Surgical  therapeutics 
should  not  be  applied  indiscriminately.  As  in  any  other  line,  conscience, 
experience  and  knowledge  are  the  best  guides. 

We  should  never  forget  that  the  extent  of  the  surgical  treatment 
must  depend  upon  the  nature  of  the  goiter.  It  is  not  enough  to  diagnose 
a  goiter  but  we  must  go  a  step  further  and  must  analyze  its  functional 
capacity.  A  hypo-active  goiter  will  be  treated  entirely  differently  from  a 
hyperactive  one.  Of  course  surgically  it  is  an  easy  matter  to  even  up  a 
neck,  to  resect  a  parenchymatous  goiter,  or  to  enucleate  a  conglomera- 
tion of  cystic  or  colloid  nodules.  From  the  esthetical  and  surgical 
point  of  view,  the  operation  is  a  success,  yet,  a  great  deal  of  harm  may 
have  been  done.  Indeed,  it  is  not  so  rare  to  find  patients  with  large 
colloid  goiters  whose  thyroid  secretion  is  barely  sufficient  to  meet  the 
physiological  purposes.  In  such  conditions  thyroidectomy  may  result 
only  in  aggravating  the  already  existing  hypothyroidism.  To  be  sure, 
enucleation  of  the  colloid  or  cystic  nodules,  in  some  of  these  patients, 
may  help  materially  the  function  of  the  thyroid  since  the  pressure  on 
the  normal  parts  of  the  gland  having  been  removed,  the  normal  paren- 


COXTRA-IXDICATIOXS  TO  OPERATION  299 

chyma  can  expand  and  resume  its  physiological  function,  so  that  a  com- 
plete restitutio  ad  integrum  of  its  functional  activity  may  follow. 

All  this  goes  to  show  that  the  question  does  not  reduce  itself  simply 
to  the  removal  of  the  enlarged  gland  no  matter  if  this  goiter  secretes 
too  much  or  too  little.  It  is  clear,  too,  that  a  correct  interpretation  and 
a  correct  therapeutic  measure,  whatever  it  may  be,  undertaken  at  the 
proper  time  and  with  judgment,  may  restore  the  normal  functional 
equilibrium  not  onlv  of  the  thyroid  but  also  of  the  entire  inner  secretory 
apparatus. 

The  most  difficult  cases  to  handle  are  those  in  which,  beside  the 
colloid  and  cvstic  nodules,  there  is  a  marked  compensatory  parenchyma- 
tous hypertrophy.  Should  we  in  such  cases  decide  to  undertake  an  ener- 
getic medical  treatment  with  iodin,  we  may  run  the  risk  of  increasing 
the  functional  activity  of  the  thyroid,  and  of  throwing  into  the  blood 
circulation  an  enormous  amount  of  thyroid  secretion  and  thereby  deter- 
mine, what  Kocher  calls,  a  "thyroid  diarrhea"  with  all  its  thyrotoxic 
consequences.  Should  we,  on  the  other  hand,  excise  the  degenerated 
portions  of  the  gland,  we  shall  at  the  same  time  remove  a  more  or  less 
large  portion  of  the  compensatorily  hypertrophied  thyroid,  and  so  pos- 
sibly expose  the  patient  to  hypothyroidism.  Such  cases  should  be  treated 
with  the  greatest  care  and  handled,  according  to  Kocher  (as  we  do,  for 
example,  suspected  cases  of  syphilis);  a  trial  treatment  with  very  small 
doses  of  iodin  should  be  given,  and  a  careful  watching  of  the  patient 
should  be  instituted.  The  decision  will  be  taken  according  to  the 
results  obtained. 

CONTRA  INDICATIONS    TO    OPERATION. 

Despite  the  most  severe  asepsis,  and  the  most  skilful  technic,  one 
runs  the  chance  of  losing  his  patient  whenever  the  goiter  has  been  of 
very  long  standing;  whenever  it  has  caused  prolonged  pressure  symp- 
toms, and  whenever  marked  bronchopulmonary  symptoms  are  present. 
The  same  dangers  exist  when  goiter  has  caused  marked  cardiac  disturb- 
ances as  myocarditis,  dilatation  of  the  heart,  increased  cardiac  action, 
in  short,  whenever  there  is  a  mechanical  or  thyrotoxic  goiter-heart. 
In  these  instances  cyanosis  of  the  face,  edema  of  the  hands  and  teet, 
even  ascites  may  be  present.  In  BasedowiHed  goiters,  where  thyrotoxi- 
cosis has  reached  an  advanced  degree,  the  chances  lor  fatal  results  have 
become  greatly  increased.  The  same  is  true  of  malignant  goiters  that 
have  involved  the  neighboring  tissues,  especially  the  trachea  ami  vinous 
trunks.  The  same  is  true  in  strumitis  when  it  has  caused  such  a  peri- 
strumitis so  as  to  involve  the  neighboring  tissues  in  a  similar  manner  as 
does  the  malignant  goiter.      In  all  these  cases  nor  only  the  results  quoad 


300  INDICATIONS  FOR  OPERATION  IN  SIMPLE  GOITER 

vitam,  but  also  the  immediate  results  are  problematic.  For  one  success, 
how  many  failures!  In  all  such  cases  one  must  rely  upon  judgment  and 
experience  as  the  best  guides. 

TREATMENT  WITH  INJECTIONS. 

I  think  it  can  be  safely  said  that  punctures  with  aspirative  needle 
and  injections  of  medicinal  substances  in  goiter  are  things  of  the  past. 
This  method  of  treatment  is  a  blind,  uncertain  and  dangerous  one.  The 
only  instances  in  which  I  think  it  is  justified  are  in  inoperable  cases  of 
exophthalmic  goiter  for  which  Porter  advised  the  injection  of  boiling 
water.  The  treatment  of  goiter  by  the  injection  method  is  not  new; 
almost  every  known  medicament  as  ergotine,  chromic  acid,  osmic  acid, 
permanganate  of  potash,  strychnine,  Fowler's  solution,  liquor  sesqui- 
chlorati,  carbolic  acid,  tincture  of  10dm,  ether,  iodoform,  glycerin 
solution,  etc.,  has  been  given  a  trial.  The  injection  of  such  substances 
is  expected  to  produce  a  local  sclerosis  and  finally  to  reduce  the  size  of 
the  goiter.  It  is  injected  directly  into  the  parenchyma  with  a  small 
syringe.  Of  course  before  injecting,  aspiration  should  be  made  in  order 
to  see  if  the  needle  has  penetrated  a  vein,  in  which  case  the  position 
of  the  needle  must  be  changed.  These  injections  are  repeated  as  often 
as  necessary.  After  a  few  months  of  similar  treatment,  in  many  instances 
the  thyroid  shrinks  in  size,  but  in  many  others  it  does  not,  or  it  does  very 
irregularly.  It  is  this  that  makes  the  method  uncertain.  Furthermore, 
the  method  is  a  dangerous  one  because  hemorrhages  and  abscesses  have 
been  known  to  follow  quite  frequently.  Sudden  dyspnea  after  such 
injections  has  been  often  reported.  Diffuse  infiltration  of  the  neighbor- 
ing tissues  has  been  noticed  more  than  once.  A  great  risk  lies  in  the 
possibility  of  injecting  the  medicament  into  a  vein.  Horsley  has  shown 
that  the  injection  of  15  c.c.  of  tincture  of  iodin  into  the  jugular  vein  of  a 
dog  caused  death. 

One  of  the  greatest  disadvantages  of  this  method  is  that  it  converts 
the  thyroid  into  a  fibrous  mass  which  afterward  not  infrequently  causes 
more  trouble  than  the  goiter  itself.  And  then,  finally  when  the  patient 
resorts  to  an  operation,  the  surgical  act  is  rendered  extremely  difficult  on 
account  of  the  fibrous  degeneration  of  the  goiter  and  its  intimate  adhe- 
sions with  the  trachea  and  other  tissues. 

All  these  inconveniences  might  be,  however,  overlooked  if  a  danger 
far  more  serious  were  not  hanging  over  the  patient's  head.  I  have  in 
mind  sudden  death.  This  is  not  a  matter  of  mere  conjecture.  Heymann 
reported  12  cases  of  death,  and  Wolfler,  in  1891,  reported  12  other  cases. 
Death  occurred  either  because  of  sudden  asphyxia  due  to  the  swelling 
of  the  goiter  on  account  of  hemorrhage  or  strumitis.    The  case  of  Bonnet 


TREATMENT  WITH  IXJECTIOXS  301 

reported  by  Vallette  will  serve  as  a  good  illustration  of  the  danger  of 
injections.  Bonnet,  a  prominent  surgeon  of  Lyon,  was  one  day  con- 
sulted by  a  young,  handsome  lady  for  goiter.  It  was  a  cyst  which  did 
not  cause  any  disturbance  whatsoever  but  greatly  distressed  the  patient 
from  an  esthetic  point  of  view.  She  wanted  to  get  rid  of  the  tumor 
without  operation  and  insisted  upon  having  the  treatment  done  by  the 
injection  method.  Tincture  of  iodin  was  used.  Everything  went  all 
right  the  two  following  days,  so  that  the  surgeon  felt  safe  in  leaving  the 
patient  and  in  going  to  the  country.  Three  days  after  Bonnet  returned. 
From  the  station  he  went  straight  to  the  patient's  house  to  see  how 
everything  was  getting  on.  To  his  horror  he  found  a  coffin  surrounded 
by  candles.  What  had  occurred  is  easily  told:  necrosis  of  the  goiter 
had  taken  place,  strumitis  had  followed,  and  suffocation  had  occurred 
so  rapidly  that  death  ensued  before  surgical  help  could  be  secured. 


THYROTOXICOSIS. 


This  condition  is  known,  too,  as  Graves'  Disease,  Basedow's  Dis- 
ease, and  Exophthalmic  Goiter.  Mavo  calls  it  hyperthyroidism,  Kocher 
calls  it  thyrotoxicosis.  Following  Kocher,  I  have  adopted  the  latter 
denomination.  My  discussion,  however,  will  have  due  regard  for  the 
classical  terminology  so  firmlv  fixed  in  the  literature  that  the  usual 
names  may  be  employed  indiscriminate!}'. 

History. — That  the  Romans  already  knew  something  about  exoph- 
thalmic goiter  is  shown  by  the  fact  that  any  contract  for  buying  or  sell- 
ing of  slaves  was  ipso  facto  invalidated  whenever  exophthalmos  was 
present.  The  Romans  mav  not  have  understood  the  thyrotoxic  symp- 
tom-complex as  a  whole,  but  thev  at  least  realized  that  there  was  a 
direct  relation  between  exophthalmos  and  a  more  or  less  marked  physi- 
cal incapacity.  They  learned  by  experience  that  a  slave  with  exoph- 
thalmos was  depreciated,  disabled,  inadequate.  It  was,  however,  not 
until  1780  that  Flajani  began  to  suspect  that  exophthalmos  was  only 
a  symptom  of  a  disease  which  he  recognized  and  described,  hence  the 
name  Morbo  de  Flajani  given  by  the  Italians  to  thyrotoxicosis.  Later 
Perry,  in  1786,  came  to  the  same  conclusions.  It  is,  however,  to  Graves, 
in  1835,  and  to  von  Basedow,  in  1843,  that  the  honor  must  be  awarded 
for  giving  a  complete  description  of  the  condition.  Since  that  time 
very  little  has  been  added  to  their  clinical  descriptions  of  the  disease. 
The  gains  made  since  concern  mostly  the  etiology,  the  pathology,  and 
the  treatment  of  that  condition. 

Graves'  Disease  is  a  condition  characterized  by  a  symptom-complex 
in  which  cardiovascular  symptoms,  thyroid  hypertrophy,  exophthalmos, 
and  tremor  are  the  predominating  factors;  these  are  called  the  cardinal 
symptoms  of  the  disease.  They  are  not  always  all  present  at  the  same 
time,  nor  are  they  all  developed  with  the  same  degree  of  intensity;  one 
or  more  of  them  may  stand  out  more  prominently  than  the  others;  one 
or  more  of  them  may  be  entirely  absent.  These  cardinal  symptoms  are 
usually  accompanied  by  a  number  of  less  important  ones  which  consid- 
ered separately  seem  to  be  of  minor  importance,  but  when  grouped 
together  acquire  a  strong  diagnostic  value. 


CHAPTER   XXI. 
CARDIOVASCULAR   SYMPTOMS. 

Cardiovascular  symptoms  in  Basedow's  disease  are  certainly 
among  the  most  important.  There  is  no  case  of  truly  active  Graves' 
disease  without  cardiovascular  disturbances.  The  Basedow  patient 
suffers  and  dies  because  of  his  heart.  Cardiovascular  disturbances 
form  a  clinical  symptom-complex  which  is  called  the  thyrotoxic  goiter- 
heart,  in  contradistinction  to  the  mechanical  goiter-heart  which  we  have 
described  in  our  stud}'  of  simple  goiter. 

The  most  constant  and  typical  of  the  cardiovascular  symptoms  seen 
in  Graves'  disease  is  tachycardia.  This  symptom  never  fails.  It  is 
characterized  by  a  long-continued  rapid  action  of  the  heart.  The  num- 
ber of  heart  beats  varies,  of  course,  with  the  condition  of  the  patient  and 
with  external  as  well  as  with  internal  influences,  but  is  always  abnor- 
mally high.  The  pulse  is  persistently  rapid  and  remains  so  for  weeks, 
months  and  even  years  with  more  or  less  marked  remissions  which, 
however,  are  never  such  as  to  render  the  pulse  normal.  Even  during 
sleep,  if  the  pulse  is  taken  gently  in  order  not  to  awaken  the  patient, 
it  is  found  high,  possibly  in  the  neighborhood  of  95  or  100,  but  very 
often  far  more  rapid.  Under  excitement,  physical  effort,  or  for  no 
apparent  reason  at  all,  the  number  of  cardiac  beats  may  vary  between 
wide  limits;  the  pulse,  for  instance,  will  rise  from  100  to  150,  180,  and 
possibly  200  in  a  very  short  time.  Sometimes  the  mere  change  of  the 
patient  from  the  lying  to  the  standing  position  is  sufficient  to  cause  the 
pulse  to  increase  materially.  Tachycardia  varies,  of  course,  during  the 
development  of  the  disease,  being  at  times  more  accelerated  than  at 
others.     Sometimes  morning  and  evening  remissions  are  seen. 

Differential  Diagnosis  of  Thyrotoxic  Tachycardia. — It  can  be  truth- 
fully said  that  tachycardia  is  a  specific  symptom  of  Graves'  disease, 
and  may  even  be  considered  as  pathognomonic  of  that  condition.  To 
be  sure,  a  rapid  heart  action  often  accompanies  the  so-called  neuroses. 

Since  patients  suffering  from  Graves'  disease  usually  show  more  or  less 
marked  nervous  disturbances,  one  might  be  tempted  at  first  to  consider 
their  tachycardia  as  caused  by  a  neurosis,  but  time  and  repeated  exami- 
nations will  show  the  difference  between  a  merely  excited  pulse  and  that 
of  Graves'  disease.  A  persistent,  high  pulse-rate  while  the  patient  is  at 
rest  in  bed  is  rare  in  pure  neurosis,  and  must  be  regarded  as  highly 
suspicious   of  thyrotoxicosis.     Those  who   are   only   nervous  will   show 


DIAGXOSIS  OF  THYROTOXIC  TACHYCARDIA  305 

great  variations  in  their  well-being;  they  will  ere  long  calm  down 
and  their  pulse-rate  will  fall  accordingly,  wThereas  the  Graves'  pulse, 
even  if  it  shows  some  variations,  does  not  calm  down  in  the  same 
proportion  as  does  the  nervous  one.  Furthermore,  the  simplv  nervous 
pulse  becomes  almost  normal  during  sleep.  As  Thomson  says,  "The 
Graves'  pulse  runs  as  fast  or  faster  than  in  fever,  by  day  and  by  night, 
and  always  in  sleep,  with  less  change  at  each  counting  over  long  periods 
than  in  any  other  complaint." 

Tachycardia  due  to  inflammatory  or  organic  changes  in  the  heart 
itself  can  be  easily  eliminated,  since  in  Graves'  disease  the  heart  is,  as  a 
rule,  functionally  but  not  organically  deranged.  It  is  true,  as  wTe  shall 
see  later  on,  that  often  murmurs  are  detected  over  the  orifices  of  the 
heart,  but  these  murmurs  are  mostly  functional  and  not  organic. 

A  quick  pulse  may  be  noticed  in  anemic  and  debilitated  patients:  but 
in  such  conditions  the  pulse  varies  in  rapidity  mostly  with  physical 
exertion,  and  as  soon  as  the  patient  has  enjoyed  rest  his  pulse-rate  falls 
accordingly.  The  rapid  pulse  seen  in  all  fevers  and  Bright's  disease 
may  be  eliminated  very  easily  if  one  takes  the  trouble  to  examine  the 
patient.  The  quick  pulse  resulting  from  the  abusive  use  of  tea,  coffee, 
tobacco,  etc.,  will  soon  be  given  its  real  significance  after  a  little 
observation. 

Tachycardia  in  thyrotoxicosis  cannot  and  should  not  be  mistaken 
for  paroxystic  tachycardia,  which  is  a  striking  entity  by  itself.  As  its 
name  indicates,  that  form  of  tachycardia  comes  on  by  paroxysms  with 
the  utmost  violence.  For  no  apparent  reason  and  during  a  period  of  abso- 
lute welfare,  the  patient  suddenly  feels  his  heart  bounding  in  his  chest, 
the  pulse  rising  to  180  to  200  beats;  the  entire  cardiac  area  trembles, 
yet  neither  anxiety  nor  pain  is  present,  and  scarcely  any  dyspnea 
I  have  seen  a  case  in  which  cyanosis  was  very  marked.  This  spell  may 
last  from  fifteen  to  twenty  minutes,  or  a  few  hours,  and  with  the  same 
suddenness  with  which  it  began,  the  paroxysm  ceases  abruptly,  and  the 
pulse  becomes  normal  again.  Weeks  or  months  may  elapse  before 
another  spell  comes  on.  Sometimes,  however,  these  paroxysms  may 
occur  at  much  more  frequent  intervals  and  may  be  of  longer  dura- 
tion; they  may  even  last  for  days.  Under  such  conditions  the  prognosis 
becomes  dubious;  organic  changes  take  place  in  the  heart,  the  cardiac 
lesions  become  uncompensated  and  terminate  by  complete  cardiac  dis- 
array. Little  is  known  about  the  etiology  of  the  paroxystic  tachycardia. 
Having  noticed  that  this  paroxystic  tachycardia  is  sometimes  accom- 
panied by  some  other  thyrotoxic  symptoms,  and  thinking  that  between 
paroxystic  tachycardia  and  disturbances  of  the  genital  apparatus,  such 
as  menstruation,  menopause,  etc.,  there  was  a  direct  relation,  M.  E. 
Savini  thought  that  paroxystic  tachycardia  could  be  caused  by  an  over- 
20 


306  CARDIOVASCULAR  SYMPTOMS 

function  of  the  thyroid,  producing  in  turn  an  ovarian  "or  testicular  insuf- 
ficiency. Hence  his  advice  to  use  ovarian  extract  for  women  and  testic- 
ular extract  for  men.  In  his  experience  the  treatment  proved  to  be 
successful.  If  thyroid  extract  was  given  the  condition  got  worse,  thus 
showing  that  paroxystic  tachycardia  might  still  be  regarded  as  a  symp- 
tom of  hyperthyroidism.  In  my  case,  however,  where  the  thyrotoxic 
symptoms  were  manifestly  present,  thyroidectomy  failed  to  have  any 
effect  on  the  paroxystic  tachycardia.  That  condition  showed  a  pro- 
gressive course  and  terminated  in  death  two  years  later. 

During  the  present  war  a  number  of  cases  of  paroxystic  tachycardia 
have  been  observed  in  soldiers  after  prolonged  fatigue.  It  was  found 
that  if  a  soldier  should  swallow  a  large  mouthful  of  firm  foodstuff,  as 
bread,  meat,  etc.,  and  if  this  was  done  at  the  beginning  of  the  spell,  the 
paroxystic  tachycardia  would  stop  at  once.  The  mouthful  of  bread 
should  be  large  enough  to  oblige  the  patient  to  make  strong  efforts  at 
deglutition.  The  idea  is  to  excite  the  vagus  nerve  so  as  to  counteract 
the  action  of  the  sympathetic. 

After  all  causes  of  rapid  heart  action  have  been  eliminated,  one  is 
then  obliged  to  fall  back  upon  tachycardia  of  thyrotoxic  origin.  This 
tachycardia  is  peculiar  on  account  of  its  striking  persistence,  and  may 
be  considered  as  a  pathognomonic  symptom.  No  other  form  of  tachy- 
cardia compares  with  it  for  long  continuance. 

The  intensity  of  the  heart  action  is,  as  a  rule,  increased.  The  heart 
is  felt  bounding  in  the  chest;  the  entire  thoracic  region  may  be  shaken 
by  the  intensity  of  the  cardiac  beat.  Sometimes  the  cardiac  impulse 
is  so  intense  that  the  entire  body  is  shaken  synchronously  with  the  heart- 
beat, especially  when  the  patient  lies  quietly,  or  is  in  a  sitting  posture. 
In  the  latter  position  this  is  most  evident  in  women,  especially  when 
wearing  hats  with  feathers  on  them,  the  feathers  then  serving  as  an 
index.  In  such  instances  one  can  count  the  pulse,  although  at  some  dis- 
tance from  the  patient.  Murray  and  others  claim  to  have  heard  the 
heart  beat  at  a  distance  of  3  or  4  feet  from  the  patient's  chest. 

Etiological  Explanation  of  Tachycardia. — Tachycardia  is  the  result  of 
an  increased  susceptibility  of  the  acceleratory  as  well  as  of  the  inhibi- 
tory system  of  the  heart,  and  of  the  diminished  tonus  of  the  peripheral 
vascular  system,  thus  causing  a  vasodilatation.  Inasmuch  as  irritation 
of  the  depressor  nerve  causes  a  marked  dilatation  of  the  bloodvessels 
of  the  thyroid,  and  since  in  turn  the  thyroid  secretion,  as  shown  by 
Asher  and  Flack,  acts  as  an  excitant  of  the  same  depressor  nerve,  we 
have  here  a  vicious  circle:  the  increased  blood  supply  increases  the  thy- 
roid function,  and  the  increased  thyroid  function  increases  the  blood 
supply  through  the  action  of  the  depressor  nerve  and  influences  the 
acceleratory  as  well  as  the  inhibitory  system. 


THYROTOXIC  HEART  307 

Palpitation. — Palpitation  is  one  of  the  most  distressing  symptoms 
experienced  by  the  patient.  Not  infrequently  it  is  the  onlv  symptom 
which  drives  the  patient  to  seek  medical  aid.  Palpitation  is  a  symptom 
quite  different  from  tachycardia,  and  should  not  be  confused  with  it. 
No  normal  individual  is  conscious  of  his  cardiac  action;  as  soon,  how- 
ever, as  he  becomes  aware  of  it,  in  other  words,  as  soon  as  he  feels  that 
he  has  a  heart,  we  say  that  he  is  suffering  from  palpitation :  he  is  becoming 
conscious  of  his  tachycardia.  It  would  be  erroneous  to  believe  that  the 
symptom,  palpitation,  is  in  direct  relation  to  the  degree  of  tachycardia. 
A  marked  degree  of  tachycardia  as  in  fever,  for  instance,  may  be  present, 
yet  the  patient  is  not  conscious  of  it  as  a  rule;  he  does  not  complain  of 
palpitation,  whereas  in  other  conditions  where  possibly  a  very  moderate 
degree  of  tachycardia  is  present,  the  patient  may  be  very  greatly  dis- 
tressed by  palpitation.  He  feels  his  heart  bounding  in  his  chest,  beating 
irregularly  and  then  rapidly,  all  in  turns,  and  all  without  the  slightest 
apparent  cause.  To  be  sure  this  condition  is  made  worse  by  excite- 
ment, physical  exertion,  intoxication,  etc.  Palpitation  comes  on  mostly 
by  spells  and  is  especially  frequent  at  night;  it  banishes  sleep,  and  keeps 
the  patient  greatly  distressed.  Sometimes  palpitation  is  dependent 
upon  the  position  occupied  by  the  patient  in  bed.  For  some  patients 
it  becomes  more  accentuated  when  lying  on  the  left  side,  and  more 
rarely  so  when  lying  on  the  back. 

Palpitation  and  tachycardia  may  sometimes  be  accompanied  by 
pain  in  the  cardiac  region  which  resembles  very  much  the  pain  seen  in 
angina  pectoris;  even  loss  of  consciousness  may  occur.  Ordinarily  such 
spells,  even  when  not  accompanied  by  loss  of  consciousness,  leave  the 
patient  in  a  state  of  complete  prostration. 

Thyrotoxic  Heart.  In  mild  forms  of  Graves'  disease  the  physical 
examination  ot  the  cardiac  apparatus  does  not  reveal  any  important 
pathological  conditions.  In  fact,  in  the  great  majority  of  these  cases 
this  physical  examination  is  negative.  However,  this  is  no  longer  true 
in  advanced  cases  of  hyperthyroidism.  There  the  findings  revealed  by 
inspection,  palpation,  percussion,  auscultation,  and  x-rays  may  be  quite 
marked. 

Inspection  shows  that  over  the  entire  cardiac  area  the  heart  beats 
are  transmitted  more  or  less  violently  to  the  anterior  wall  of  the  chest; 
sometimes  the  entire  thorax  is  shaken  synchronously  with  the  cardiac 
contractions. 

Palpation  of  the  heart  shows  the  presence  of  a  thrill  over  the  cardiac 
area.  It  shows,  too,  that  the  apex  heat  m  Graves'  disease  is  usually 
forcible,  sudden,  bounding  and  rather  diffuse,  and  a  beat  can  be  felt 
farther  to  the  left  without  there  being  necessarily  an  increase  in  the 
actual  cardiac  outlines. 


30S  CARDIOVASCULAR  SYMPTOMS 

Percussion  shows  that  the  cardiac  area  may  be  greatly  enlarged;  in 
some  instances  the  volume  of  the  heart  may  attain  very  large  dimen- 
sions as  is  confirmed  by  the  x-rays.  The  increased  volume  of  the  heart  is 
caused  chiefly  by  dilatation  which  may  affect  both  chambers  and  auricles, 
but  seems  to  predominate  over  the  left  heart.  Of  course  a  certain 
amount  of  concomitant  hypertrophy  may  be  present  at  the  same  time. 
Cardiac  dilatation  is  not  permanent,  but  retrocedes  in  direct  propor- 
tion to  the  improvement  of  the  patient's  condition.  This  can  be  con- 
firmed by  repeated  clinical  as  well  as  by  skiagraphic  examinations. 

Auscultation  often  reveals  the  presence  of  a  murmur  which  is  mostly 
localized  over  the  base  of  the  heart  and  from  there  irradiates  toward 
the  other  orifices.  Its  maximum  of  intensity  is  found  generally  over  the 
pulmonary  valve,  and  is  systolic  in  character.  Not  infrequently  such 
murmurs  are  so  intense  that  they  may  be  felt  with  the  hand  over  the 
cardiac  area;  they  then  form  what  is  known  as  a  thrill.  These  murmurs, 
when  very  marked,  may  at  first  give  the  impression  that  severe  cardiac 
lesions  are  present,  yet  their  localization  at  the  base  of  the  heart,  and 
the  rapidity  with  which  they  disappear,  or  at  least  ameliorate  as  the 
patient's  condition  improves,  show  that  we  have  to  deal  not  with  organic, 
but  with  functional  disturbances  of  the  valvules.  They  seem  to  be 
mostly  dependent  upon  the  dilatation  of  the  cardiac  chambers,  causing 
in  turn  an  insufficiency  of  the  cardiac  valves.  To  be  sure,  organic 
cardiac  disturbances  may  be  present,  but  these  cases  are  in  the  minority. 
Even  a  systolic  murmur  at  the  mitral  valve  accompanied  by  an  accen- 
tuation of  the  second  pulmonary  tone  does  not  necessarily  mean  that 
we  have  to  deal  with  a  mitral  insufficiency. 

X-rays  are  a  very  valuable  adjunct  in  estimating  the  volume  of  the 
heart;  they  are  far  superior  to  any  other  means. 

In  Basedow's  disease  the  cardiac  fibers  seem  to  be  particularly  weak 
and  easily  exhausted.  The  thyrotoxic  poison,  whatever  it  is,  seems  to 
have  a  special  affinity  for  the  cardiac  muscular  elements.  This  may 
possibly  explain  the  cardiac  dilatation  so  often  met  with  in  Graves' 
disease.  That  in  the  majority  of  the  cases  we  have  to  deal  with  a  dila- 
tation, instead  of  a  cardiac  hypertrophy,  is  shown  by  the  fact  that  after 
an  operation,  or  after  the  process  has  been  healed  by  some  medical 
means,  the  limits  of  the  heart  have  a  tendency  to  return  to  normal.  In 
some  instances  the  cardiac  dilatation  may  become  acutely  marked  in  a 
short  time;  it  is  then  accompanied  not  only  by  murmurs  over  the  entire 
cardiac  area,  but  also  by  tricuspid  insufficiency,  venous  pulse,  conges- 
tion of  the  liver,  spleen,  kidneys,  edema  of  the  limbs,  ascites,  etc.  It 
follows  from  Puesch's  researches,  that  in  Basedow's  disease,  although 
the  work  of  the  heart  in  toto  is  manifestly  increased,  the  systolic  cardiac 
output   is   lower   than    in    normal   conditions.      This   latter   fact    might 


THYROTOXIC  PULSE  309 

explain,  too,  the  mode  of  origin  of  cardiac  dilatation.  Indeed,  the  mus- 
cular fibers  being  under  the  influence  of  the  thyrotoxic  poisons  on  the 
one  hand,  and  the  systolic  output  of  blood  being  diminished  on  the  other 
hand,  it  becomes  impossible  for  the  heart  to  expel  from  its  chambers  the 
amount  of  blood  which  has  flowed  into  it,  hence  dilatation.  To  be  sure, 
a  certain  amount  of  hypertrophy  nearly  always  accompanies  dilatation, 
yet  this  is  not  always  the  case,  as  instances  are  seen  where  before  death 
an  increased  volume  of  the  heart  is  present,  and  where  after  death 
postmortem  reveals  a  small,  contracted  heart.  These  cases  of  cardiac 
dilatation  without  some  degree  of  concomitant  hvpertrophv,  in  other 
words,  the  cases  of  non-compensated  dilatation  have  a  very  bad  prog- 
nosis. Hypertrophy,  when  present,  involves  mostly  the  left  ventricle; 
however,  all  the  other  chambers  participate  in  a  lesser  degree  with  that 
hypertrophy. 

Even  in  cases  of  marked  arrhythmia  and  other  cardiac  disturbances, 
the  microscopic  examination  has  failed  in  the  great  majority  of  cases 
to  reveal  any  microscopic  lesions.  At  the  most,  fatty  degeneration  and 
browTn  atrophy  have  been  found. 

Thyrotoxic  Pulse. — Sphygmographic  curves  of  the  Graves'  pulse  show 
that  it  has  all  the  characteristics  of  the  pulsus  celer.  It  is,  as  a  rule,  of 
smaller  volume,  soft,  and  often  dicrotic.  Like  the  other  symptoms,  this 
pulse-rate  varies  with  the  exacerbations  of  the  disease,  with  physical 
exertion,  mental  excitement,  or  with  or  without  anv  apparent  reason 
at  all.  Its  rhythm,  as  a  rule,  is  dependent  upon  the  cardiac  rhythm, 
yet  this  is  not  always  true,  because  if  one  auscultates  the  heart  while 
taking  the  pulse,  he  may  find  an  irregular  pulse,  while  the.  heart  action 
on  the  whole  is  regular  though  rapid.  This  only  means  that  the  cardiac 
muscle  is  incapable  of  transmitting  each  impulse  to  the  periphery. 
Why:  Is  it  purely  on  account  of  muscular  weakness?  Possibly  so  in 
some  instances,  but  not  always.  This  pulse  arrhythmia  may  be  due  to 
extrasystoles,  as  is  shown  by  electrocardiograms.  According  to  Herring, 
these  extrasystoles  are  caused  by  an  irregular  cardiomuscular  impulse 
determined  by  some  disturbances  in  the  cardiac  nervous  system.  There 
can  be  no  doubt  that  in  a  great  many  instances  the  pulse  irregularities 
are  of  nervous  origin.  In  Basedow's  patients  these  irregularities  are  so 
often  dependent  upon  the  nervous,  psychic  condition  of  the  pa  tit  n  t 
and  they  follow  so  closely  their  fluctuations,  that  it  is  impossible  not  to 
recognize  an  etiological  relation  between  them  and  these  irregularities. 
1  his  is  so  true  that  one  can  find  great  variations  in  the  pulse-rate  of  a 
Basedow  patient  inside  of  a  very  few  minutes.  I  have  not  infrequently 
seen  a  pulse-rate  fall  from  125  to  <;o  while  taking  the  pulse  and  drawing 
the  patient's  attention  to  something  else.  In  some  patients  the  pulse- 
rate  varies  with  each  respiration.     A  nervous  origin,  however,  cannot  be 


310  CARDIOVASCULAR  SYMPTOMS 

ascribed  to  the  pulsus  irregularis  perpetuus.  It  is  of  cardiac  origin  and 
caused  by  myocarditis. 

At  any  rate,  be  it  what  it  may,  a  constant  cardiac  arrhythmia  is  of  bad 
prognosis;  it  shows  that  the  strength  of  the  heart  is  reduced,  and  since 
in  Basedow's  disease  the  heart  is  the  organ  mostly  endangered,  we  must 
consider  arrhythmia,  when  present,  as  a  very  important  prognostic  symp- 
tom; it  shows  that  the  cardiac  mechanism  is  out  of  gear  and  nearing 
exhaustion.  It  does  not  necessarily  follow  that  cardiac  muscular  weak- 
ness and  insufficiency  must  always  be  accompanied  by  arrhythmia.  One 
would  indeed  meet  with  disappointment  if  he  should  regard  a  heart  as 
strong  and  safe  because  it  beats  regularly.  Once  in  a  great  while,  one 
will  venture  into  a  surgical  operation  and  be  absolutely  deceived  as  to  the 
real  value  of  the  cardiac  muscle;  the  heart  is  regarded  as  capable  of 
standing  the  surgical  strain,  and  yet,  when  the  time  comes,  there  is  not 
even  a  show  of  a  fight;  the  heart  simply  quits.  On  the  other  hand,  a 
slight  degree  of  arrhythmia  is  not  an  absolute  contra-indication  to  opera- 
tion. Nothing  is,  indeed,  more  difficult  to  judge  than  the  strength  of 
the  heart.  We  must  consequently  grasp  every  information  we  can  get 
in  order  to  draw  safe  conclusions.  Therefore  we  must  consider  cardiac 
arrhythmia,  even  slight,  as  a  very  good  warning  symptom:  it  would  be 
unpardonable  not  to  give  it  its  due  consideration. 

Test  of  Functional  Capacity  of  the  Heart. — For  more  than  four  years 
I  have  applied  the  Katzenstein  test  with  great  satisfaction.  This  test  is 
as  follows:  Both  femoral  arteries  are  firmly  compressed  with  the  fingers 
below  Poupart's  ligament  until  pulsations  are  suppressed.  The  blood- 
pressure  and  pulse-rate  are  recorded  before,  and  again,  after  pressure 
on  the  arteries  has  been  applied  from  two  to  three  minutes.  With  a 
sound  heart  the  blood-pressure  is  found  higher  afterward,  and  the 
pulse  slower.  If  the  blood-pressure  and  the  pulse  have  not  changed, 
this  shows  that  the  heart  is  not  quite  normal,  but  not  actually  incom- 
petent. If  blood-pressure  remains  the  same,  but  the  pulse  increases, 
this  shows  a  higher  degree  of  insufficiency.  If  the  blood-pressure  is 
found  lower  and  the  pulse-rate  higher,  this  warns  us  of  severe  functional 
cardiac  disturbances.  Their  seventy  is  in  proportion  to  the  extent  of 
the  drop  in  the  blood-pressure  and  of  the  increase  in  the  pulse  beat. 
When  the  test  shows  marked  functional  insufficiency,  Katzenstein 
advises  against  any  operation,  unless  the  indications  are  vital,  and  then 
only  under  local  anesthesia.  I  have  found  the  Katzenstein  test  very 
accurate  and  valuable.  Every  time  cardiac  postoperative  complications 
occurred,  the  Katzenstein  test  made  before  had  been  positive. 

Blood-pressure  is,  as  a  rule,  of  medium  strength  and  varies  between 
ioo  and  150.     A  high  blood-pressure  is  unusual. 


CHAPTER   XXII. 
BASEDOW   STRUMA. 

The  enlargement  of  the  thyroid  gland  in  Basedow's  disease  is  another 
of  the  most  important  cardinal  symptoms;  it  is  the  one  which  in  true 
exophthalmic  goiter  seldom  fails.  This  is  so  true  that  Kocher  has  said, 
"No  goiter,  no  Basedow's  disease."  Such  a  dogmatic  statement  suffers 
exceptions,  however,  since  in  certain  cases  even  the  most  expert  is 
unable  clinically  to  determine  with  certainty  whether  there  is  an  enlarge- 
ment of  the  thyroid  gland  or  not,  vet  at  the  operation,  one  is  almost 
alwavs  astonished  to  find  the  gland  larger  than  normally.  As  a  general 
principle,  it  may  be  said  that  whenever  the  thyrotoxic  clinical  complex 
is  present,  there  is  always  at  some  stage  or  another  during  the  course 
of  the  disease  hyperplasia  of  the  thyroid.  This  hyperplasia  may  not 
be  detectable  clinically,  but  is  present  microscopically,  as  we  shall  see 
later  on  when  studying  the  pathology  of  the  thyrotoxic  gland.  In  cases 
in  which  hyperplasia  of  the  thyroid  is  apparently  absent,  if  a  careful 
retrospective  history  is  taken,  one  will  find,  as  a  rule,  that  there  has 
been  thyroid  enlargement  at  one  time  or  another.  It  must  not  be 
forgotten  that  thyroid  enlargement  is  liable  to  undergo  great  fluctuations, 
that  it  may  be  more  marked  at  times  than  at  others,  that  it  may  even 
show  up  only  quite  a  long  time  after  the  other  thyrotoxic  symptoms 
have  appeared.  I  can  recall  a  few  cases  in  which  the  thyroid  enlargement 
became  detectable  clinically  only  months  after  the  other  symptoms  of 
Graves'  disease  were  well  established. 

At  any  rate  one  thing  is  certain:  the  volume  of  the  thyroid  is  not  at 
all  proportionate  to  the  severity  of  the  disease.  It  is  not  the  largest  goiter 
that  causes  the  most  symptoms;  sometimes  most  severe  cases  of  Graves' 
disease  are  seen  where  very  little,  or  no  apparent  enlargement  of  the 
thyroid  gland  is  present,  whereas  large  goiters  are  often  accompanied 
by  little,  or  no  thyrotoxic  symptoms. 

I  hyrotoxicosis  may  develop  in  patients  whose  thyroid  gland  has 
been  previously  normal,  or  in  ones  previously  affected  with  goiter,  what- 
ever it  may  be,  colloid,  cystic,  or  malignant.  In  the  first  cases,  the 
exophthalmic  goiter  is  called  primary:  in  the  second  case  it  is  called 
secondary  or  Basedoicified  goiter. 

The  exact  distinction  between  primary  and  secondary,  or  Basedow  i- 
fied  goiter,  is  m  certain  cases  difficult,  and  sometimes  even  impossible. 
Of  course,   in   a   great   main    instances,   the   distinction   is   easy.       I  ake, 


312  '  BASEDOW  STRUMA 

for  instance,  a  young,  nervous,  woman,  who  never  had  anything  the 
matter  with  her  neck,  and  who  after  emotion,  worry,  overwork,  or  some 
acute  infection,  develops  a  rapid  heart  action,  palpitation,  tremor, 
insomnia,  exophthalmos  with  Graefe,  Stellwag  and  Moebius  symptoms, 
and  who  at  the  same  time  shows  an  enlargement  of  the  thyroid  with 
vascular  symptoms  developed  in  it.  Here  no  one  would  hesitate;  this 
is  a  primary  thyrotoxic  goiter,  because  the  enlargement  in  this  case  has 
occurred  in  a  gland  which  was  previously  absolutely  normal.  Take,  on 
the  other  hand,  another  patient  who  has  had  for  many  years  a  cystic 
or  colloid  goiter  which  never  caused  very  much  trouble,  except  possibly 
some  pressure  symptoms.  Suddenly  or  gradually,  with  or  without  any 
apparent  cause,  this  patient  becomes  nervous,  complains  of  palpita- 
tion, tremor,  shows  exophthalmos,  and  in  short,  exhibits  a  train  of 
symptoms  which  are  unmistakably  thyrotoxic.  This  is  a  secondary 
thyrotoxic  goiter  because  previous  to  this  condition  the  patient  has  had 
for  years  a  harmless  goiter.  This  simple  goiter  has  become  a  Basedowi- 
fied  one.  These  distinctions,  however,  are  not  always  so  simple.  There 
are  cases,  indeed,  of  secondary  exophthalmic  goiter  in  which  the  thy- 
roid gland  has  become  of  such  a  thyrotoxic  type,  that  unless  the  case 
has  been  seen  previously,  it  is  no  longer  possible  to  say  offhand  whether 
the  case  is  primary  or  secondary.  The  physician  will  then  have  to  rely 
entirely  upon  the  history  of  the  case. 

One  may  think  the  distinction  between  these  two  forms  of  goiter 
devoid  of  interest.  Therein  lies  a  mistake,  for  the  distinction  between  the 
primary  and  the  secondary,  or  Basedowified  goiter,  is  of  great  clinical 
and  prognostic  value.  A  Basedowified  goiter  will  respond  to  surgical 
treatment  far  more  readily  and  safely  than  a  primary  one. 

The  volume  of  the  thyrotoxic  goiter  is  exceedingly  variable.  In  the 
primary  form  the  hyperplasia  is  diffuse  and  involves  both  lobes,  the 
isthmus,  and  the  pyramidal  process.  It  is  true  that  cne  lobe  may  be 
affected  more  than  the  other.  In  that  case  the  larger  lobe  will  rarely 
exceed  twice  the  size  of  a  goose  egg,  and  the  right  lobe  will  be  more 
often  involved  than  the  left.  In  the  secondary  form,  or  Basedowified 
goiter,  the  goiter  may  have  all  kinds  of  dimensions:  the  volume  in  this 
form  depends  upon  the  size  of  the  preexisting,  non-toxic  goiter,  whether 
it  be  colloid  or  cystic,  and  to  it,  of  course,  we  must  add  the  thyrotoxic 
hyperplasia  and  hypertrophy  of  the  remaining  normal  parenchyma  of 
the  gland. 

The  consistency  of  the  thyrotoxic  goiter  depends  largely  upon  the 
variety  of  goiter  with  which  we  have  to  deal,  and  with  the  stage  of  the 
disease.  In  the  early  beginning  of  the  primary  form  and  sometimes  in 
the  regressing  period  of  the  disease  the  gland  is  mostly  soft,  but  as 
soon  as  thyrotoxicosis  is  well  established  the  goiter  becomes  firm   and 


VASCULAR  SYMPTOMS  OF  THE  THYROID  313 

elastic,  while  in  advanced  conditions  it  becomes  of  much  harder  consis- 
tent". In  the  last  stage  where  the  gland  has  become  exhausted  and  is 
undergoing  a  cirrhosis,  it  is  truly  hard.  In  the  Basedowified  goiter,  of 
course,  the  consistency  will  depend  upon  the  nature  of  the  preexisting 
goiter;  the  gland,  however,  will  show  more  firmness  to  the  touch  than 
during  the  non-toxic  period. 

Pressure  over  the  thyrotoxic  goiter,  especially  in  the  early  stage  of 
its  development,  is  painful;  this  is  a  very  good  diagnostic  point. 

The  surface  of  the  primary  thyrotoxic  goiter  is  finely  granular.  This 
sensation  is  given  by  the  distended  alveoli  bulging  under  the  capsule 
of  the  thyroid  gland.  In  the  secondary  form  the  surface  is  nearly  always 
nodular  and  depends  upon  the  surface  and  form  of  the  preexisting 
goiter. 

The  true  primary  exophthalmic  goiter  very  seldom  causes  marked 
dyspneic  symptoms,  since  its  size  is  not  great  enough  to  cause  compres- 
sion of  the  trachea.  Pressure  symptoms,  however,  may  occur  when  the 
lobes  extend  posteriorly  and  inwardly  so  as  to  form  a  circular  goiter 
around  the  trachea.  In  the  great  majority  of  cases  the  shortness  of 
breath  which  is  often  complained  of  by  Basedow  patients  is  mostly  of 
nervous  and  cardiac  origin.  In  the  Basedowified  form  of  exophthalmic 
goiter,  of  course,  the  shortness  of  breath  is  more  apt  to  be  of  mechanical 
origin,  being  caused  by  the  size  of  the  goiter  itself.  Vascular  symptoms 
play  their  part,  too,  since  they  increase  the  size  of  the  goiter  and  thus 
increase  the  pressure. 

More  than  the  normal  thyroid,  the  thyrotoxic  goiter  is  apt  to  be 
influenced  by  the  various  physiological  processes  of  the  organism  such  as 
menstruation,  pregnancy,  etc.  The  goiter  reacts  then  by  a  more  or  less 
marked  temporary  enlargement  which  retrocedes  as  soon  as  the  process 
is  over.  Hence  the  complaint  is  often  heard  that  the  neck  gets  larger 
at  each  menstruation,  pregnancy,  etc.  Psychic  disturbances  such  as 
anger,  fright,  etc.,  have  the  same  effect.  At  such  times  the  vascular 
symptoms  of  the  thyroid  may  become  so  marked  that  the  subjective 
symptoms  such  as  shortness  of  breath,  sensation  of  constriction  in  the 
neck,  etc.,  are  more  evident. 

Vascular  Symptoms  of  the  Thyroid. — The  exophthalmic  form  of  goiter 
is  above  all  a  vascular  goiter.  This  feature  has  been  observed  by  every- 
one who  has  had  experience  with  Graves'  disease.  \  ascular  symptoms 
are  of  great  diagnostic  value.    They  consist  chiefly  of: 

1.  Pulsation  oj  the  thyroid. 

2.  Thrill. 

3.  Murmurs. 

These  symptoms  may  be  seen,  of  course,  in  the  non-toxic  vascular 
goiter,  but  the  latter  type  will  not  be  mistaken  for  a  thyrotoxic  goiter, 


314  BASEDOW  STRUMA 

since  no  symptoms  of  thyrotoxicosis  will  accompany  it.  If  they  do,  it 
is  no  longer  a  simple  vascular  goiter,  but  a  thyrotoxic  vascular  goiter. 
It  goes  without  saying  that  the  simple  vascular  goiter  may  become 
thyrotoxic,  as  shown  by  A.  Kocher.  In  the  few  really  vascular  goiters 
which  I  have  seen,  the  vascular  symptoms  were  all  that  I  could  detect. 
The  patients  had  none  of  the  thyrotoxic  symptoms  found  in  Graves' 
disease.  Vascular  symptoms  may  be  found,  too,  in  simple  goiter.  Here, 
however,  an  examination  made  with  care  will  reveal  that  this  simple 
goiter  is  undergoing  thyrotoxic  changes.  In  other  words,  it  is  becoming 
a  secondary  exophthalmic  or  Basedowified  goiter.  The  vascular  symp- 
toms, consequently,  retain  a  great  diagnostic  significance.  They  are,  of 
course,  not  always  present,  and  when  present,  may  vary  in  intensity. 

Simple  inspection  will  reveal  an  intense  pulsation  of  the  entire  gland 
and  of  the  whole  cervical  region;  the  carotids  beat  violently  and  the  thy- 
roid is  the  site  of  a  marked  pulsation.  In  severe  cases  it  is  not  infrequent 
actually  to  see  the  enlarged  and  tortuous  branches  of  the  superior  thy- 
roid artery  beating  under  the  skin.  The  gland  in  certain  cases  can  be 
compared  to  a  vascular  sponge  which  can  be  squeezed  at  will,  and  by 
so  doing,  reduced  considerably  in  size. 

The  vascular  thyrotoxic  goiter  expands  like  an  aneurysm.  This 
expansive  pulsation  must  not  be  mistaken  for  the  transmitted  one.  Indeed, 
sometimes  one  may  think  that  he  has  to  deal  with  an  expansive  pulsa- 
tion, when  the  gland  is  only  displaced  en  ??iasse,  forward  and  backward, 
by  the  violent  carotid  beats.  The  pulsation  of  the  thyroid  gland  is 
then  only  a  transmitted  one.  The  best  way  to  determine  whether  pul- 
sation is  expansive  or  transmitted  is  to  grasp  the  whole  gland  in  the  palm 
of  the  hand  and  to  exert  a  moderate  compression.  The  gland  will  then 
be  felt  expanding  as  in  an  aneurysm.  If  no  expansion  is  felt,  the  pulsa- 
tion is  then  a  transmitted  one. 

Very  often,  especially  in  thin  patients,  a  venous  pulse  is  present;  it  is 
soft  and  is  not  synchronous  with  the  cardiac  pulse.  It  occurs  mostly 
in  the  median  and  jugular  veins.  This  venous  pulse  is  nearly  always 
negative.  In  rare  cases,  however,  it  may  be  positive  and  is  then  directly 
transmitted  from  the  heart  on  account  of  the  insufficiency  of  the  tri- 
cuspid valve.  It  has  been  said  that  a  positive  venous  pulse  may  be 
caused  by  a  direct  transmission  of  the  arterial  beat  through  the  thin 
walls  of  the  venous  trunks. 

Palpation  with  the  thumb  over  the  thyroid  gland  and  especially  over 
its  vascular  poles  will  reveal  the  presence  of  a  thrill,  while  auscultation 
over  the  same  regions  will  reveal  the  presence  of  murmurs.  These  mur- 
murs vary  in  intensity  and  are  more  or  less  musical  in  character,  and  as 
a  rule,  systolic;  rarely,  they  are  continuous  and  when  they  are  so,  they 
show  an  exacerbation  of  tone  during  the  systole.    These  murmurs  may 


PATHOLOGY  AND  HISTOLOGY  OF  THYROTOXIC  GOITER        315 

be  heard  all  over  the  gland  but  acquire  their  maximum  of  intensity  at 
the  vascular  poles  of  the  thyroid,  especially  the  superior  ones,  while 
often  they  are  heard  only  there.  If  they  are  not  so  easily  heard  over 
the  inferior  thyroids,  it  is  because  these  vessels  lie  deep,  whereas  the 
superior  ones  are  more  superficial.  If  an  ima  artery  is  present,  the 
svstolic  murmur  will  be  heard  over  it  also.  These  murmurs  may  be 
heard  over  the  large  veins  in  the  supraclavicular  regions;  they  are  then 
continuous  and  resemble  the  "bruit-de-none." 

The  bloodvessels  in  thyrotoxic  goiter  are  exceedingly  thin  and  friable. 
This  condition  will  explain,  partly  at  least,  why  operations  for  exoph- 
thalmic goiter  are  usually  more  bloody  than  operations  for  simple 
goiter.  This,  however,  is  not  the  only  reason,  because  we  shall  see  that 
the  blood  of  Basedow  patients  contains  an  increased  amount  ot  anti- 
thrombin,  and  for  this  reason  its  coagulability  is  diminished. 


PATHOLOGY    AND    HISTOLOGY    OF   THYROTOXIC    GOITER. 

Although  Lubarsch  and  Marchand,  in  1896,  and  Askanazy,  in  1898, 
recognized  some  of  the  microscopic  peculiarities  of  thyrotoxic  goiter, 
it  is  really  to  A.  Kocher  and  to  L.  B.  Wilson  that  we  owe  our  knowledge, 
not  only  of  the  pathological  changes  in  the  thyroid,  but  also  of  their 
real  significance.  They  have  brought  this  question  to  its  real  focus; 
and  it  is  they  who  have  established  the  true  relation  between  the  clinical 
symptoms  and  the  pathological  findings. 

The  thyrotoxic  gland  when  seen  in  situ,  as  during  operation,  is  often 
surrounded  by  a  layer,  more  or  less  thick,  of  loose  connective  tissue, 
which  renders  it  adherent  to  the  neighboring  tissues,  especially  the  wind- 
pipe and  the  carotid  sheath.  The  condition  resembles  that  one  seen 
after  treatment  with  the  .v-rays,  or  the  one  which  follows  a  mild  degree 
of  thyroiditis.  This  production  of  the  connective  tissue  is  most  likely 
due  to  a  chronic  irritation  caused  by  the  thyrotoxin,  and  has  been 
regarded  bv  some  as  proof  in  favor  of  the  infectious  origin  ot  Graves 
disease. 

On  the  cut  surface  the  primary,  thyrotoxic  goiter  is  dry,  gray,  or 
yellowish  gray,  and  exudes  very  little  or  no  secretion  at  all.  1  he  most 
interesting  features,  however,  are  the  microscopic  ones.  Hiese  pecu- 
liarities may  be  summarized  in  the  following  manner: 

1.  The  alveoli  are  increased  in  size  and  number  ami  this  increase  is 
in  proportion  to  the  severity  of  the  disease.  They  have  lost  then  round 
or  oval  shape  and  have  become  irregular  and  polyform  1  Fig.  63).  I  Ins 
irregularity  is  intended  to  increase  the  lining  capacity  of  the  alveoli  in 
order  to  accommodate  the  increased  number  oi  epithelial  cells. 


31G 


BASEDOW  STRUMA 


2.   In  normal  alveoli  the  epithelium  lining  their  walls  is  low  cuboidal. 
In  thyrotoxic  conditions  the  epithelium    becomes  cubic,    highly  cylin- 


FlG.  63. — Thyrotoxic  goiter.     Note  the  polyhedric  form  of  the  alveoli. 


•  ••••    ^ 

jt       - 


Fig.  64. — Thyrotoxic  parenchymatous  goiter  and  high  cylindrical  epithelium  forming 
two  layers  in  places.     No  colloid  in  the  alveoli.      X  280. 

drical  (Fig.  64),  affects  the  columnar  type,  and  increases,  not  only  in 
size,  but  also  in  number.     Sometimes  cellular  hypertrophy  and  hyper- 


PLATE    VIII 


*-\-  ~^j»m 


Leukocytic  Infiltration  with  Germinal   Centers  in  a  Thyrotoxic 
Parenchymatous  Goiter.     X  46. 


PATHOLOGY  AND  HISTOLOGY  OF  THYROTOXIC  GOITER        317 

plasia  are  so  marked  that  the  epithelium  can  no  longer  line  the  walls 
of  the  alveoli  in  one  continuous  layer,  but  is  then  forced  to  bulge  out 
and  give  rise  to  papillary  formations  in  order  to  make  room  for  every 
cellular  element.  Even  this  may  not  be  sufficient  since  proliferation 
may  be  so  marked  that  the  epithelium  has  to  dispose  itself  in  two  or 
three  layers,  one  lying  on  top  of  the  other;  sometimes  the  alveoli  are 
entirely  filled  with  epithelium  only.  In  some  instances  proliferation 
ma)'  be  so  intense  that  the  epithelial  cells  do  not  even  attempt  to  shape 
themselves  into  alveoli;  they  lie  without  order,  thus  giving  rise  to  micro- 
scopic pictures  very  similar  to  those  of  malignant  adenoma.  The 
protoplasma  of  the  thyrotoxic  cells  is  clearer  than  the  normal  ones; 
their  nuclei  are  basal  and,  as  a  rule,  are  not  very  much  larger  than  the 
normal.  As  shown  by  McCallum,  mitosis  is  quite  frequent,  a  sign  which 
must  mean  an  increased  glandular  activity.  \  ery  often  a  number  of 
desquamated  cells  undergoing  cytolysis  are  found  floating  looselv  in  the 
lumen  of  the  alveoli.  This  desquamation  and  cytolysis  are  alwavs  o.c 
ill  omen,  so  far  as  prognosis  is  concerned. 

3.  In  normal  thyroids  as  well  as  in  simple  goiters  the  colloid  is 
thick  and  stains  readily.  In  thyrotoxic  goiters  the  colloid  is  thin  and 
takes  the  stain  with  difficulty,  or  not  at  all.  Ischenschmid  has  shown 
that  this  fluid  colloid  takes  the  stain  differently  from  the  normal  colloid. 
It  becomes  eosin-red  with  the  Haemalaun-eosin  stain,  whereas  the 
thick  colloid  found  in  simple  goiters  or  normal  thyroids  becomes  blue 
or  red.  This  may  be  regarded  as  a  good  proof  that  this  colloid  is  chemi- 
cally different  from  the  normal  one.  It  thus  becomes  easy  to  understand, 
too,  that  colloid  in  thyrotoxic  goiters,  being  far  more  fluid  and  thin  than 
the  normal,  will  be  that  much  more  readily  absorbable. 

4.  In  simple  colloid  goiters  small  foci  of  leukocytes  are  sometimes 
found  here  and  there  throughout  the  stroma  of  the  gland;  in  normal 
thyroids  nothing  of  the  kind  is  seen.  In  Graves'  disease,  on  the  con- 
trary, they  are  very  frequent  and  numerous;  these  leukocytic  foci  recall 
the  formation  of  a  lymph  node.  Not  infrequently  they  have  a  clear, 
plain  germinal  center.  (Plate  VIII.)  The  significance  of  these  leuko- 
cytes is  not  clear.  They  are  considered  by  some  as  belonging  to  the 
status  lymphaticus,  and  by  some  others  as  a  proof  of  a  chronic  irritation 
by  the  thyrotoxin,  and  would  be,  in  other  words,  the  equivalent  of  a 
chronic  thyroiditis. 

Now  comes  the  important  question:  Are  the  microscopic  changes 
found  in  thyrotoxic  goiter  constant,  and  specific  of  the  disease?  I  do 
not  think  that  I  could  do  better  than  to  quote  verbatim,  L.  B.  Wilson: 
"By  assuming  that  the  symptoms  of  true  exophthalmic  goiter  are  the 
results  of  an  excretion  from  the  thyroid,  and  by  attempting  to  deter- 
mine the  amount  of  such  excretion  from  pathological  data,  one  is  able 


318  BASEDOW  STRUMA 

to  estimate  in  a  large  series  of  cases  the  clinical  changes  of  the  disease 
with  about  80  per  cent,  of  accuracy,  and  the  clinical  severity  of  the  dis- 
ease with  about  75  per  cent,  of  accuracy.  It  would  therefore  appear 
that  the  relationship  of  primary  hypertrophy  and  hyperplasia  of  the 
parenchyma  of  the  thyroid  to  true  exophthalmic  goiter  is  as  direct  and 
as  constant  as  a  primary  inflammation  of  the  kidney  to  the  symptoms 
of  Blight's  disease.  Any  considerable  findings  to  the  contrary  I  believe 
to  indicate  either  inaccurate  or  incomplete  observations  on  the  part  of 
the  pathologist  or  clinician,  or  both." 

I  can  but  subscribe  to  this  statement.  In  the  great  majority  of  my 
cases  I  was  able  to  determine  quite  accurately  the  severity  of  the  dis- 
ease by  simply  looking  at  the  slides,  being  careful  not  to  know  before- 
hand from  what  patient  they  came.  In  a  certain  number  of  cases  I 
was  surprised  not  to  find  the  characteristic  changes,  or  not  to  find  them 
in  proportion  to  the  severity  of  the  disease.  If  new  sections,  however, 
were  made  of  different  portions  of  the  excised  gland,  then  the  charac- 
teristic pathological  changes  could  be  found  in  places,  thus  supporting 
fully  Kocher's  statement  that  thyrotoxic  hyperplasia  may  be  localized 
to  circumscribed  areas.  These  Basedow  islands  may  be  either  the 
beginning  of  microscopic  changes  which  are  going  to  involve  the  whole 
gland,  or  they  may  be  the  remainder  of  a  regressive  process  which  is 
going  to  transform  the  thyrotoxic  goiter  into  a  colloid  goiter.  We  must 
always  bear  in  mind  that  in  the  natural  course  of  things,  if  the  patient 
lives  long  enough,  the  thyrotoxic  goiter  is  destined  to  become  a  colloid 
one.  Inasmuch  as  during  the  thyrotoxic  stage,  the  gland  is  burning 
itself  up,  if  the  process  lasts  long  enough,  exhaustion  is  bound  to  come. 
The  gland  enters  the  regressive  period;  connective  tissue  gradually 
invades  and  takes  the  place  of  the  noble  elements,  and  what  remains  of 
the  alveoli  becomes  colloid  in  type.  These  two  processes,  namely  col- 
loid regression  and  cirrhosis  of  the  gland,  are  bound  to  depreciate  and 
diminish  the  secreting  power  of  the  gland,  hence  hypothyroidism; 
hence  myxedema.  We  may,  consequently,  say  that  a  Basedow  patient, 
if  he  is  not  killed  meanwhile  by  his  thyrotoxicosis,  is  logically  destined 
to  become  myxedematous,  provided,  of  course,  the  toxic  process  lasts  long 
enough. 

In  the  secondary  or  Basedowified  goiter,  the  same  pathological  find- 
ings characteristic  of  Graves'  disease  will  be  found.  They  will  be  most 
developed  at  the  periphery  of  the  gland  and  at  the  vascular  poles. 

It  is  true  that  sometimes  in  young  individuals,  and  especially  at  the 
time  of  puberty,  hyperplastic  islands  similar  to  those  seen  in  thyrotoxi- 
cosis, will  be  found  spread  throughout  the  normal  parenchyma.  They 
may,  of  course,  have  a  thyrotoxic  signification;  it  is  not,  however, 
always  necessarily  so,  because  they  may  be  interpreted  as  some  non- 
toxic proliferation  of  the  thyroid. 


CHAPTER   XXIII. 
OCULAR   SYMPTOMS. 

The  ocular  symptoms,  especially  exophthalmos,  have  always  been 
among  the  most  striking  features  of  Graves'  disease;  they  are  the  symp- 
toms which  from  the  earliest  times  have  struck  the  attention  not  only 
of  the  medical  profession,  but  also  of  the  laity.  They  are  the  features, 
too,  from  which  the  disease  has  taken  its  distinguishing  names:  as,  for 
example,  exophthalmic  goiter,  Glotzaugenkrankheit,  Morbo  esoftahnico, 
etc.,  just  as  if  the  ocular  pathology  alone  seemed  to  constitute  the  whole 
disease.  By  ocular  symptoms  we  refer  to  a  group  of  symptoms,  some 
involving  the  globus  oculi  itself,  some  others  the  eyelids,  and  again 
others  taking  their  origin  in  a  distorted  coordination  of  the  orbital  mus- 
culature. These  symptoms  are  exophthalmos  and  the  Dallrymple,  Graefe, 
Stellzvag,  Kocher,  and  Moebius  symptoms. 

Exophthalmos. — Exophthalmos,  though  one  of  the  cardinal  symp- 
toms of  Graves'  disease,  yet  is  not  so  constant  as  some  of  the  other 
clinical  symptoms.  Usually  it  appears  when  once  the  disease  is  already 
established;  exceptionally,  however,  it  may  appear  at  the  onset  of  the 
disease  as  the  first  manifestation.  Sometimes  it  never  shows  up  at 
all.  Unlike  the  other  symptoms  seen  in  thyrotoxicosis,  exophthalmos  is 
very  much  less  subject  to  fluctuations.  Even  when  all  the  other  thyro- 
toxic symptoms  undergo  material  improvement,  exophthalmos  may  show 
little  or  no  change.  It  is  the  most  stubborn  and  the  most  discouraging 
of  all  the  features  of  Graves'  disease.  Even  years  after  everything  else 
has  almost  entirely  subsided,  exophthalmos  still  remains  as  the  living 
witness  of  the  past  thyroid  pathology. 

Exophthalmos  is  best  seen  in  profile,  although  in  ordinary  casts,  the 
front  view  will  reveal  the  conditions  just  as  well.  It  takes  place  directly 
forward,  following  the  axis  of  the  orbita.  Exophthalmos,  as  a  rule, 
affects  both  eyes.  It  may  be  more  marked  in  one  eye  than  in  the  other 
and  in  the  rarer  cases,  it  may  be  purely  and  primarily  unilateral 
(Fig.  65). 

Unilateral  Exophthalmos,  however,  is  not  such  a  rarity  after  all. 
Sattler  was  able  to  find  lO<;  cases  in  the  literature.  In  4^  cases  the 
exophthalmos  was  on  the  right  side;  in  40  casts  it  was  on  the  left,  while 
m  the  remaining  23  cases  the  side  was  not  given.     Furthermore,  Sattler 


320 


OCULAR  SYMPTOMS 


found  that  in  43  cases  of  unilateral  exophthalmos,  17  times  the  exoph- 
thalmos was  on  the  same  side  on  which  the  thyroid  hyperplasia  was 
most  developed,  14  times  on  the  right  side,  and  3  times  on  the  left 
side,  while  in  6  cases  the  unilateral  exophthalmos  was  developed  on  the 
opposite  side  to  the  one  on  which  the  thyroid  development  was  most 
marked. 


Fig.  65. — Unilateral  exophthalmos. 


Fig.  66. — Bilateral  exophthalmos. 


Bilateral  Exophthalmos. — A  bilateral  exophthalmos  may  become  uni- 
lateral in  the  course  of  the  disease,  and  this  is  especially  true  when  an 
operation  on  the  thyroid  such  as  a  ligation,  or  unilateral  lobectomy,  has 
been  performed.  When  that  is  the  case,  exophthalmos,  as  a  rule,  dis- 
appears on  the  side  corresponding  to  the  one  which  has  been  operated 
on.  However,  this  retrocession  of  exophthalmos  is,  as  a  rule,  only 
temporary;  the  exophthalmos  returns  to  its  previous  intensity. 

The  degree  of  exophthalmos  is  extremely  variable  and  may  fluc- 
tuate, although  in  less  degree  than  the  other  thyrotoxic  symptoms,  with 
the  period  of  the  disease,  with  the  physical  and  mental  condition  of  the 
patient,  or  with  no  apparent  reason  whatsoever.  It  becomes  most  inten- 
sive during  periods  of  exacerbation  of  the  disease,  and  during  excite- 
ment (Fig.  66).  The  degree  of  exophthalmos  is  not,  as  a  rule,  in  pro- 
portion to  the  severity  of  the  disease,  since  it  may  be  extremely  marked 
in  light  cases  of  thyrotoxicosis,  and  scarcely  apparent  in  severe  cases  of 
Graves'  disease.  In  some  cases  the  protrusion  of  the  eves  is  so  marked 
that  the  patient  can  no  longer  bring  the  upper  eyelid  into  contact  with 
the  lower.     They  remain  apart  so  that  a  portion  of  the  eyeball  is  seen 


BILATERAL  EXOPHTHALMOS  321 

through  the  half-closed  lids,  and  this  is  especially  true  during  sleep, 
because  at  that  time  no  voluntary  effort  intervenes.  Some  authors,  as 
Trousseau,  Zimmerman,  Rehn  and  Tucker,  have  reported  cases  of  com- 
plete dislocation  of  the  eyeball,  and  Deschamps  and  Perriol  have 
described  a  case  in  which  the  eyeball  had  completely  bulged  out  of  the 
orbital  cavity,  and  in  which  necrosis  of  the  cornea  had  followed. 

Not  infrequently,  the  degree  of  exophthalmos  is  so  slight  that  it  is 
difficult  to  decide  whether  it  is  pathological  or  not.  This  is  not  uncom- 
mon with  large,  protruding  eyes,  yet  such  people  may  not  have  the 
slightest  sign  of  Graves'  disease.  It  is  that  much  more  difficult  to  decide 
whether  the  apparent  protrusion  is  pathological  or  not,  since  the  relations 
between  the  globus  oculi  and  orbita  vary  greatly,  not  only  with  each 
individual,  but  also  in  the  same  patient  when  both  sides  are  compared. 
It  is  only  after  comparing  photographs  of  the  patient  taken  before  and 
after  his  thyrotoxic  condition,  and  by  taking  into  consideration  the 
statements  of  the  immediate  members  of  his  family,  that  judgment  can 
be  passed. 

A.  Kocher  and  Sattler  undertook  to  establish  what  were  the  normal 
relations  of  the  eyeball  to  the  orbita,  using  for  that  study  the  exophthal- 
mometer  of  Birsch-Hirschfeld.  The)'  found  that  in  many  cases  the 
globus  oculi  would  protrude  more  than  normally,  vet  no  one  could  say 
that  exophthalmos  was  present.  As  soon,  however,  as  there  was  at 
the  same  time  an  enlargement  of  the  palpebral  fissure,  then  onlv  did 
exophthalmos  become  apparent. 

In  some  cases  auscultation  over  the  protruding  eyes  has  betrayed 
the  presence  of  murmurs  which  have  been  interpreted  by  several  authors 
as  being  of  vascular  origin.  E.  Herring  demonstrated,  however,  that 
these  murmurs  heard  over  the  eyeball  were  of  muscular  origin.  They 
are  heard  only  when  the  eyelids  are  shut,  increase  in  proportion  to  the 
intensity  of  the  occlusion  of  the  eyelids,  and  disappear  as  soon  as  the 
muscular  contraction  ceases.  These  murmurs  resemble  the  placental 
murmurs  heard  in  pregnant  women;  they  are  also  found  in  normal  indi- 
viduals. They  seem  to  have  sometimes  a  decided  systolic  character,  and 
may  then  be  partly  in  relation  to  the  increased  vascularization  of  the 
orbita. 

Usually  the  ocular  movements  in  Basedow  patients  are  not  materi- 
ally hampered;  it  is,  however,  not  so  rare  to  find  a  diminution  of  the 
upward  and  downward  amplitude  of  movement.  This  is  very  likely  due 
to  the  fact  that  the  eyeball,  being  pushed  forward,  lias  its  center  of  rota- 
tion displaced;  hence  the  disturbance  in  the  ocular  mechanism.  Curi- 
ously enough,  even  marked  exophthalmos  causes  little  or  no  discomfort 
to  patients.  All  that  they  may  complain  of  is  the  sensation  of  a  forward 
pushing  of  both  eyes. 

21 


322 


OCULAR  SYMPTOMS 


Eyelid  Symptoms. — Under  this  name  we  understand  several  symp- 
toms peculiar  to  Graves'  disease,  yet  not  pathognomonic  and  not 
always  constant.  These  are  the  Dallrymple,  Graefe,  Kocher  and  Stell- 
wag  symptoms. 

Dallrymple  Symptom. — In  order  to  be  normal,  the  palpebral  fissure 
must  meet  certain  requirements  (Fig.  67).  In  normal  conditions  the 
superior  eyelid  covers  a  small  portion  of  the  cornea,  whereas,  the  lower 
eyelid  reaches  the  edge  of  the  cornea.  In  Graves'  disease  the  angle  of 
aperture  is  greatly  increased;  both  eyelids  are  farther  apart,  leaving 
uncovered  not  only  the  cornea,  but  also  a  greater  or  smaller  portion  of  the 
sclerotica.  This  abnormal  enlargement  of  the  palpebral  fissure  is  called 
the  Dallrymple  symptom.  This  finding  is  entirely  independent  of  the 
exophthalmos  itself  since  it  is  often  present,  as  shown  by  the  exophthal- 
mometer,  when  little  or  no  protrusion  of  the  eyes  can  be  found.     Vice 


Fig.  67. — Normal  eye. 


versa,  we  may  have  a  very  marked  exophthalmos  with  a  normal,  or  only 
moderate,  enlargement  of  the  palpebral  fissure.  In  the  majority  of 
cases,  however,  it  is  this  pathologically  enlarged  palpebral  fissure 
which  creates  the  impression  that  we  have  to  deal  with  a  marked 
protrusion  of  the  eyes. 

Enlargement  of  the  palpebral  fissure  does  not  necessarily  mean  that 
we  have  to  deal  with  a  thyrotoxic  condition,  since  it  is  often  found  in 
normal  individuals.  We  know  that  normally  some  people  have  very 
large,  prominent  eyes,  and  that  some  others  have  very  small  ones.  This 
fact  depends  greatly  upon  the  degree  of  enlargement  of  the  palpebral 
fissure. 

Graefe  Symptom. — The  head  being  kept  immobile  and  looking  for- 
ward and  slightly  upward,  the  patient  is  asked  to  fix  his  eyes  upon  an 
object,  such  as  the  finger  of  the  examiner  or  a  pencil  moving  slowly 


KOCHER  SYMPTOM  323 

downward.  Under  normal  conditions  the  upper  lid  follows  the  downward 
rotation  of  the  globus  oculi  until  the  movement  is  terminated.  There 
is,  consequently,  coordination  between  these  two  movements,  namely, 
between  the  downward  rotation  of  the  eyeball  and  the  downward  fol- 
lowing of  the  upper  eyelid.  In  Graves'  disease,  however,  the  upper 
eyelid  indeed  begins  the  downward  movement,  but  does  not  finish  it; 
it  stops  while  the  eyeball  still  continues  to  rotate  downward.  This  is 
the  Graefe  symptom.  It  is  due  to  a  spastic  retraction  of  the  upper  eve- 
lid.  In  certain  cases  not  only  does  the  upper  eyelid  stop,  but  it  even 
retracts  suddenly  upward.  When  the  downward  rotation  is  completed, 
if  the  eyeball  is  kept  in  that  position  for  a  time,  the  upper  eyelid  may 
then,  too,  follow  and  complete  its  downward  excursion.  If,  however, 
the  upper  eyelid  should  not  take  its  full  downward  course  and  remain 
retracted  at  a  certain  height,  then  when  the  globus  oculi  begins  to  rotate 
upward,  the  eyeball  moves  alone  for  a  time,  and  only  after  a  while  does 
the  eyelid  start  its  upward  movement.  The  Graefe  symptom  is  not 
dependent  upon  the  degree  of  exophthalmos  itself,  since  it  is  found  in 
cases  where  no,  or  little,  exophthalmos  is  present.  As  with  the  Dall- 
rvmple  sign,  so  the  Graefe  symptom  is  sometimes  the  earliest  indication 
of  the  disease.  It  may  be  present  or  more  developed  on  one  side  than 
on  the  other.  In  some  individuals  it  may  be  present,  or  disappear  under 
certain  given  conditions.  For  instance,  Kocher  was  able  to  detect  it 
only  when  the  patient  was  in  the  lying  position.  It  may  be  present  at 
times  and  not  at  others,  hence  the  necessity  of  numerous  attempts  at 
searching  for  this  symptom. 

The  sign  of  Graefe  when  accompanied  with  some  other  thyrotoxic 
symptoms  becomes  of  great  diagnostic  value;  it  may  even  be  considered 
as  pathognomonic.  It  must  be  remembered,  however,  that  in  certain 
normal  individuals,  the  Graefe  symptom  may  be  positive.  It  has  been 
found,  too,  in  certain  diseases  of  the  nervous  system  such  as  hysteria, 
neurasthenia,  epilepsy,  myasthenia,  paralysis  agitans,  and  bulbar  paraly- 
sis of  the  eyes.  In  these  cases  we  shall  scarcely  mistake  one  condition 
for  the  other;  consequently  the  Graefe  symptom  in  Basedow's  disease 
retains  its  full  diagnostic  value. 

Kocher  Symptom.  While  the  point  of  a  pencil,  or  a  finger  is  held  in 
front  of  the  patient,  on  a  horizontal  plane  with  the  line  of  vision,  and  the 
head  is  kept  immobile,  the  patient  is  asked  to  follow  with  his  eyes  this 
pencil  or  ringer  point  in  its  very  sudden  and  abrupt  upward  movement. 
In  normal  individuals  the  upper  eyelid  will  follow  synchronously  the 
upward  rolling  of  the  globus  oculi.  In  Basedow's  patients  this  may  not 
be  so.  The  upper  lid  may  contract  itself  and  rise  slightly  before  the 
globus  oculi  has  started  its  upward  movement.  The  incoordination  of 
these  two  movements  is  called  the  Kocher  symptom.     It  may  be  consul- 


324  OCULAR  SYMPTOMS 

ered  as  a  modification  of  the  Graefe  symptom,  but  may  be  present  when 
the  latter  is  totally  absent.  Its  etiological  and  pathological  significance 
is  the  same  as  that  of  the  Dallrymple  and  Graefe  symptoms. 

Stellwag  Symptom. — In  normal  individuals  the  winking  of  the  eye- 
lids occurs  from  three  to  ten  times  a  minute.  In  Basedow  patients  the 
number  of  these  winks  is  markedly  diminished.  Sometimes  there  is 
scarcely  one  wink  taking  place  during  a  whole  minute,  while  even  two  or 
three  minutes  may  elapse  before  any  sign  of  winking  is  observed.  This 
fact  known  as  the  Stellwag  sympton,  was  first  described  by  C.  H.  Stellwag 
in  1869.  It  is  quite  frequent  and  was  considered  by  Stellwag  as  of 
great  diagnostic  importance.  But  its  diagnostic  value  has  certainly 
been  exaggerated  because  sometimes,  and  even  in  the  most  severe  cases 
of  Basedow's  disease,  it  fails  to  be  present.  Indeed,  in  some  cases  the 
winking  of  the  eyelids  instead  of  being  diminished,  is  increased  in 
number. 

Moebius  Symptom. — In  Basedow's  disease  the  insufficiency  of  the 
converging  power  of  the  eye  may  be  quite  marked.  The  attention  was 
called  to  this  symptom  by  Moebius,  hence  the  name.  It  was,  however, 
also  observed  by  Trousseau  in  1862.  The  Moebius  symptom  is  observed 
in  the  following  manner:  an  object  such  as  a  finger  or  a  pencil  is  placed 
at  a  certain  distance  before  the  patient,  horizontally  with  the  line  of 
vision,  and  between  the  eyes.  The  patient  is  then  asked  to  concentrate 
his  look  upon  that  object  while  it  is  brought  nearer  and  nearer  until 
convergence  is  necessary  to  see  it  still  with  both  eyes.  In  normal  indi- 
viduals convergence  may  attain  a  marked  degree  before  complaint  is 
made,  whereas  in  Graves'  disease  the  convergence  cannot  be  kept  up. 
As  soon  as  it  has  reached  a  certain  degree,  which  varies  with  each  indi- 
vidual, convergence  ceases;  one  of  the  eyes  diverges,  taking  at  once  the 
previous  position  parallel  to  the  line  of  vision,  while  the  other  eye  still 
continues  to  converge  and  look  at  the  object.  This  divergence  consti- 
tutes the  Moebius  symptom.  The  insufficiency  of  convergence  is  not  at 
all  in  proportion  to  the  degree  of  exophthalmos,  since  it  may  be  extremely 
marked  in  cases  where  the  protrusion  of  the  eyes  is  only  moderate.  It 
will  be  easily  understood,  however,  that  a  marked  exophthalmos  can 
but  increase  the  difficulty  of  converging.  According  to  Sattler,  when 
all  sources  of  error  have  been  eliminated,  the  Moebius  symptom  in  Graves' 
disease  is  not  so  frequent  after  all.  It  should  be  considered  as  of  thy- 
rotoxic origin  only  when  the  refraction  of  both  eyes  has  been  controlled, 
skiagraphically  or  functionally. 

The  Moebius  symptom  is  explained  in  the  following  manner  by 
Landstrom:  when  the  rectus  internus  muscle  contracts  itself,  it  rotates 
the  globus  oculi  inward,  thus  putting  the  outer  portion  of  the  Landstrom 
muscle  on  the  stretch.    Since  this  muscle  in  Basedow's  disease   is   per- 


STARIXG  LOOK  325 

manently  and  pathologically  contracted,  it  hinders  the  action  of  the 
rectus  internus,  and  renders  the  convergence  painful,  hence  causing  the 
divergence  of  one  of  the  eyes. 

The  pupils,  as  a  rule,  are  not  affected  in  Graves'  disease.  Numerous 
statistics  show  that  in  a  very  small  percentage  of  thyrotoxic  cases,  they 
may  be  either  dilated,  contracted,  or  unequal.  None  of  these  troubles, 
however,  seems  to  be  dependent  upon  the  Basedow  condition. 

The  power  of  accommodation  of  the  eye  is  not  disturbed  either,  for 
even  in  marked  exophthalmos  the  power  of  vision  is  not  altered.  Intra- 
ocular alterations  such  as  papillitis,  optic  neuritis,  and  optic  nerve  atro- 
phy have  rarely  been  seen. 

Nystagmus  is  seldom  found  in  Basedow. 

Lacrymal  Secretion. — There  is  sometimes  an  exaggerated  produc- 
tion of  tears  which  occurs  without  the  presence  of  conjunctivitis,  inflam- 
mation of  the  lacrymal  ducts,  or  any  other  cause  whatsoever.  This 
exaggerated  secretion  of  tears  occurs  by  spells,  and  often  during  the 
night.  Sometimes  in  advanced  cases  of  Graves'  disease  there  is  a  hvpo- 
secretion.  These  disturbances  are  very  likely  due  to  a  neurosis  of  the 
secretory  apparatus  of  the  lachrymal  ducts.  They  might  possibly  be 
due,  too,  to  some  alterations  of  the  lacrymal  glands  themselves. 

On  account  of  the  diminution  of  the  sensibility  of  the  cornea  and 
conjunctiva,  and  on  account  of  the  protrusion  of  the  eyeballs,  and 
because  of  their  diminished  protection  caused  by  the  eyelid  symptoms, 
and  furthermore  on  account  of  the  infrequence  of  the  winkings  of  the 
eyelids,  the  eyes  remain  exposed  more  than  normally  to  numerous 
injuries  which  in  some  conditions  may  lead  to  very  severe  ocular  com- 
plications and  inflammations  such  as  conjunctivitis  and  keratitis. 
When  they  occur  these  complications  are  peculiarly  stubborn  to  treat- 
ment, and  the  reason  may  possibly  be  because  they  are  partly  due  to 
some  trophoneurosis. 

Staring  Look. — Now  that  we  have  studied  all  the  ocular  and  eyelid 
symptoms,  we  shall  be  better  able  to  understand  the  peculiar  staring 
and  glaring  look  which  is  so  characteristic  of  Graves'  disease,  and  which 
possibly  more  than  any  other  symptom,  has  always  impressed  the 
laity.  The  eyes  in  Graves'  disease  have  a  look  of  fixity,  of  great  surprise, 
and  sometimes  of  wild  anger  or  terror,  which  has  been  called  the 
"tragic  stare"  (Fig.  66).  At  the  same  time  the  eyes  have  always  a 
peculiar  brilliancy,  a  fact  which  has  been  observed  since  antiquity. 
The  Germans  call  it  the  "Glanzaugen."  A  number  of  conditions  concur 
to  give  birth  to  this  staring  and  glaring  look.  The  enlarged  palpebral 
fissure,  the  exophthalmos,  and  the  diminished  winking  of  the  eyes  are 
the  most  important  intervening  factors.  Under  such  conditions  not 
only  do  the  eyes  protrude,  bur  also  a  portion,  more  or  less  great,  of  the 


326  OCULAR  SYMPTOMS 

sclerotica  is  exposed,  thus  leaving  a  white,  unprotected  surface.  Add 
to  this  the  fact  that,  on  account  of  the  Dallrymple  symptom,  the  eyes 
are  less  shadowed  by  the  eyelashes;  that,  on  account  of  the  Stellwag 
svmptom,  the  white  sclerotica  and  the  shining  cornea  form  a  glaring 
surface  which  is  seldom  interrupted  by  the  winking  of  the  eyelids,  and 
finallv,  that  the  increased  lacyrmal  secretion  cannot  but  add  materially 
to  the  brilliancy  of  the  eyes  by  increasing  the  moisture  all  over  their 
surface,  then  all  these  various  factors  will  make  us  understand  the 
pathogenesis  of  the  staring  look. 

Edema  and  Pigmentation  of  the  Eyelids. — Once  in  a  while,  true  edema 
of  the  evelids  is  observed.  In  some  instances,  however,  this  swelling  of 
the  evelids  does  not  pit  on  pressure,  and  is  due,  according  to  Eppinger 
and  Sattler,  to  a  deposit  of  fat,  as  is  shown  by  postmortems.  It  is 
strange,  indeed,  to  see  fatty  tissue  deposited  there  when  it  has  disap- 
peared from  all  other  regions  of  the  body.  Not  so  rarely,  the  eyelids 
are  highly  pigmented,  thus  forming  a  large,  brown-black  circle  around 
the  eyes.  In  severe  cases  this  pigmentation  is  very  marked  and  may 
coincide  with  pigmentation  of  other  organs  of  the  body.  It  is  one  of 
the  cutaneous  manifestations  in  Basedow's  disease,  and  is  probably  of 
suprarenal  body  origin. 

Etiology  of  Exophthalmos. — The  pathogenesis  of  exophthalmos  is  a 
subject  which  has  proved  of  great  interest,  and  at  the  same  time,  a  great 
puzzle  to  the  scientists,  who  from  the  earliest  beginnings  of  the  knowl- 
edge of  Graves'  disease  have  tried  to  explain  its  etiology.  In  trying  to 
explain  the  cause  of  exophthalmos  one  should  not  forget  the  following 
facts,  namely:  That  if  exophthalmos,  as  a  rule,  develops  slowly  and 
gradually,  it  may  nevertheless  develop  rapidly;  it  is  furthermore  sub- 
ject to  fluctuations  varying  with  the  physical  and  mental  condition  of 
the  patient.  It  may  subside  entirely  after  operation,  and  on  the  same 
day  of  the  operation,  to  reappear  again  a  few  days  after.  All  this  is 
said  to  emphasize  the  liability  of  exophthalmos  to  rapid  changes.  This 
fact  being  first  agreed  upon,  then  at  once  a  number  of  theories  which 
have  been  advanced  in  explanation  of  the  etiology  of  exophthalmos 
must  be  discarded.  Ipso  facto  this  is  true  of  the  theory  which  was 
upheld  by  Jeandrassik  and  Mendel,  namely,  that  exophthalmos  is 
caused  by  abnormal  deposit  cf  retrobulbar  fat.  The  same  is  true  for 
Cooper's  and  Egberg's  theory  which  claimed  that  exophthalmos  is  due 
to  the  fatty  degeneration  of  the  recti  muscles  of  the  orbita,  and  for 
Miiller's  theory  claiming  that  exophthalmos  is  due  to  a  serous  infiltra- 
tion of  the  retrobulbar  connective  and  fatty  tissues  of  the  orbita  on 
account  of  vasomotor  disturbances  caused  by  thyrotoxicosis.  If  this 
edema  should  really  exist,  there  would  be  no  reason  why  it  should  not 
extend  to  the  evelids.     It  is  true  that  sometimes  edema  of  the  evelids 


ETIOLOGY  OF  EXOPHTHALMOS  327 

is  found  in  Graves'  disease,  but  this  is  far  from  constant.  Furthermore, 
these  different  theories  are  not  at  all  supported  by  the  findings  of  post- 
mortems which  have  been  made  by  a  number  of  authors  and  mvself. 
Macroscopic  as  well  as  microscopic  examination  of  the  entire  orbita 
failed  to  reveal  either  an  excess  of  fat,  an  edema,  a  passive  congestion, 
or  a  fatty  degeneration  of  the  recti  muscles.  Furthermore,  such  theories 
do  not  permit  one  to  understand  intelligently  the  rapid  fluctuations  seen 
in  exophthalmos.  These  theories  do  not  suit.  Some  other  explanation 
must  be  found. 


Fig.  68. — Sagittal  cut  through  eyelid  and  eye:  I,  tarsal  cartilage;  z,   Mailer's  muscle; 
3,  eyelid;  4,  levator  palpebra  superioris;  5,  rectus  muscle;  6,  cornea. 


In  1858  Heinrich  Miiller  described  a  layer  of  unstriped  muscula- 
ture located  in  the  inferior  portion  of  the  orbita,  and  in  the  following 
year  he  described  another  layer  in  the  superior  portion  of  the  orbita; 
this  muscle  has  since  been  known  as  \1  filler's  muscle.  In  the  upper  lid 
it  is  formed  bv  a  thin  layer  of  unstriped  muscular  fibers  running 
(Fig.  68)  from  the  terminal  palpebral  insertion  of  tin-  musculus  levator 
palpebral  superioris  to  the  upper  convex  border  of  the  tarsal  cartilage, 
into  which  it  terminates  directly,  or  through  tin-  means  of  elastic  fibers. 
This  muscular  layer  is  about  10  millimeters  in  length  and  of  varying 
thickness.  In  the  lower  lid  these  unstriped  muscular  fibers  extend 
from  the  conjunctival  fornix  to  the  border  of  the  lower  tarsal  cartilage. 
The  description  of  this  muscle  has  been  revised  by  man}    authors,  as 


328  OCULAR  SYMPTOMS 

Sappey,  Testut,  Merkel  and  others,  and  found  correct.  This  muscle  has 
no  direct  relation  whatsoever  to  the  eyeball.  It  is  an  eyelid  muscle:  it  will 
consequently  be  easy  to  understand  that  this  thin  muscle  can  have  no 
effect  whatsoever  upon  the  globus  oculi,  therefore  any  theory  holding 
that  this  muscle  is  the  cause  of  exophthalmos  must  fall.  It  can  produce 
eyelid  symptoms,  but  not  exophthalmos. 

Graefe,  Sattler  and  McKenzie  have  thought  that  exophthalmos 
might  be  caused  by  an  intense  active  and  passive  venous  congestion  of 
the  orbita.  As  said  before,  postmortems  failed  to  show  any  support  for 
this  theory.  Furthermore,  if  this  were  true,  we  should  expect  to  find 
this  passive  as  well  as  active  congestion  confined,  not  only  to  the  orbita 
itself,  but  also  to  the  veins  in  direct  communication  with  the  orbital 
veins,  through  the  nasofrontal  and  supra-orbital  veins  communicating 
with  the  ophthalmic  veins.  There  should  be,  too,  a  venous  stasis  of 
the  retina.      But  there  are  no  such  things. 

Many  authors,  as  Fuchs,  Mannheim,  Krause,  A.  Kocher  and  others, 
have  sought  to  explain  exophthalmos  by  claiming  that  there  was  a  marked 
dilatation  of  all  the  arteries  of  the  orbita,  caused  by  the  thyrotoxic 
condition,  and  possibly  through  direct  stimulation  of  the  sympathetic 
nerve.  As  Landstrom  rightfully  remarks,  this  theory  is  hardly  accept- 
able. It  is  scarcely  conceivable  that  we  should  have  such  a  localized 
arterial  dilatation  so  developed  as  to  cause  sometimes,  not  only  a  marked 
exophthalmos,  but  even  a  dislocation  of  the  globus  oculi.  If  such  were 
the  case,  we  should  certainly  expect  to  find  a  pulsating  exophthalmos, 
which  even  in  the  most  pronounced  cases  is  never  observed. 

Landstrom  thought  that  he  had  solved  the  problem  when  he  described 
a  new  unstriped  muscle.  In  making  seriated  microscopic  slides  of 
the  entire  content  of  the  orbita,  he  demonstrated  the  existence  of 
unstriped  fibers  taking  their  origin  in  the  septum  orbitale,  and  taking 
their  insertion  on  the  equator  of  the  globus  oculi.  This  muscle  forms  a 
shallow  cone  which  holds  the  eyeball  in  suspension.  According  to  this 
same  author,  since  this  unstriped  musculature  is  supplied  by  the  sym- 
pathetic nerve,  the  explanation  of  exophthalmos  is  a  clear  one.  It  is 
due,  he  thinks,  to  a  constant  permanent  contraction  of  Landstrom's 
muscle  on  account  of  the  permanent  thyrotoxic  excitation  of  the  sympa- 
thetic nerve.  Certainly  this  theory  is  one  of  the  most  satisfactory 
ever  advanced.  But,  although  it  may  explain  the  mild  cases  of  exoph- 
thalmos, it  nevertheless  fails  to  give  a  satisfactory  explanation  for  the 
cases  in  which  protrusion  of  the  eyes  is  so  marked  as  to  cause  disloca- 
tion of  the  eyeball.  Under  such  conditions  Landstrom's  muscle  can- 
not be  considered  as  an  etiological  factor,  because,  since  it  takes  its 
origin  on  the  septum  orbitale  and  its  insertion  on  the  equator  of  the 
eyeball,  it  would  be  able  to  lift  the  eye  out  of  the  orbita  only  as  far  as 


ETIOLOGY  OF  EXOPHTHALMOS  329 

the  level  septum  orbitale  and  no  farther.  The  portion  of  the  eye  behind 
the  equator  ocuh  still  remains  in  the  orbita.  There  must  consequently 
be  some  other  factors  which  still  remain  to  be  discovered. 

The  problem  would  be  solved  if  any  musculature  had  been  found  in 
Tenon's  capsule.  This,  to  my  knowledge,  has  not  been  demonstrated. 
If  it  were,  since  Tenon's  capsule  is  indirectly  attached  to  the  septum 
orbitale  through  the  fibrous  expansion  of  the  striped  muscles  of  the 
orbita,  it  would  then  be  easy  to  understand  that  any  contraction  of  this 
membrane  would  throw  the  eyeball  forward.  Furthermore,  there  would 
be  no  difficult}'  in  explaining  any  degree  of  exophthalmos  up  to  disloca- 
tion of  the  eyeball.    This,  however,  still  remains  to  be  demonstrated. 

That  the  sympathetic  intervenes  as  an  active  and  potent  factor  in 
the  production  of  exophthalmos  there  can  be  no  doubt.  Claude  Ber- 
nard and  many  authors  have  shown  that  the  excitation  of  the  cervical 
portion  of  the  sympathetic  produces  an  enlargement  of  the  palpebral 
fissure  and  exophthalmos.  It  has  been  said  that  exophthalmos  is  due  to 
the  mechanical  irritation  of  the  sympathetic  nerve  by  the  hyperplastic 
goiter.  Although  this  might  be  possibly  true  in  some  cases,  we  must 
sav,  however,  that  if  hyperplasia  of  the  thyroid  in  itself  plays  a  mechani- 
ical  part  by  irritating  the  sympathetic  nerve,  this  part  must  be  a  small 
one,  and  is  not  a  constant  one,  since  the  relief  afforded  to  the  ocular 
symptoms  by  lobectomy  or  ligation,  is,  although  sometimes  striking  and 
occurring  as  soon  as  the  operation  is  performed,  only  temporary,  as  a 
rule.  Usually,  one,  two,  or  three  days  after  the  operation,  exophthal- 
mos returns  to  its  previous  intensity.  It  is  true  that  the  supposedly 
mechanical  irritant  still  remains  in  situ  after  ligation,  but,  even  when 
it  has  been  removed,  as  after  thyroidectomy,  the  ocular  symptoms  are 
nevertheless  still  present.  Furthermore,  large,  simple,  malignant  and 
inflammatory  goiters,  tumors  of  the  cervical  lymph  nodes,  very  seldom 
produce  any  mechanical  involvement  of  the  sympathetic  nerve.  Why 
should  the  thyrotoxic  goiter  alone  have  that  privilege  r  The  truth  of 
the  matter  is  that  the  thyrotoxic  poison  acts  electively  upon  the  sympa- 
thetic system,  thus  acting  as  an  irritant.  The  sympathetic  disturb- 
ances are,  however,  in  the  great  majority  of  cases,  secondary  and  not 
primary,  as  some  internists  like  to  believe. 

One  thing  still  remains  to  be  explained:  Why  is  it,  that  even  after 
all  the  other  thyrotoxic  symptoms  have  subsided,  exophthalmos  still 
persists  for  a  long  time,  and  sometimes  for  good?  Most  likely  because 
the  eyeball  having  been  protruded  for  so  long  a  time  has  lost  its  "right 
of  domicile"  in  the  orbita:  ir  has  acquired  new  relationships:  connective 
tissue  and  retrobulbar  fat  have  filled  the  dead  space  hit  by  the  eyeball 
when  protruding,  hence  the  difficulty  or  even  impossibility  tor  the 
globus  ocuh  ever  to  return  to  its  previous  normal  anatomy. 


330  OCULAR  SYMPTOMS 

The  Graefe,  Kocher,  and  Dallrymple  symptoms  are  easily  explained; 
they  are  due  to  the  irritation  of  the  sympathetic  nerve  which  supplies 
Miiller's  muscle.  As  seen  before,  this  thin  layer  of  unstriped  mus- 
culature in  the  upper  lid  extends  from  the  termination  of  the  levator 
palpebral  to  the  upper  border  of  the  tarsal  cartilage;  in  the  lower  lid 
it  extends  from  the  conjunctival  fornix  to  the  tarsus.  Consequently, 
the  contraction  of  these  two  little  muscles  will  retract  both  eyelids  and 
will  enlarge  the  palpebral  fissure;  it  will  explain,  too,  the  cramp-like 
retraction  of  the  eyelids.  Possibly  Sattler's  explanation  of  the  Graefe 
symptom  may  be  partly  true  also.  He  claims  that  it  is  due  to  inco- 
ordination between  the  centers  of  the  musculus  levator  palpebral 
superioris  and  those  commanding  the  up-and-down  movements  of  the 
globus  oculi.  This  theory,  of  course,  would  explain  the  incoordination 
between  these  two  movements,  but  would  not  explain  the  sudden  retrac- 
tion which  often  takes  place  in  the  upper  eyelid  while  the  globus  oculi 
is  rolling  downward. 

It  has  been  said  that  the  eyelid  symptoms  are  caused  by  an  exag- 
gerated tonus  of  the  musculus  levator  palpebral  superioris.  I  fail  to 
see  why  we  should  have  an  increased  tonicity  of  this  unstriped  muscle 
alone,  when  we  all  know  that  in  Graves'  disease  the  striped  muscula- 
ture is  anvthing  but  braced  up:  the  sudden  giving  way  of  the  knees  is 
the  best  proof  of  that.  In  my  judgment  the  orbicularis  palpebral  does 
not  plav  any  part  in  the  production  of  eyelid  symptoms. 


CHAPTER   XXIV. 
MUSCULAR   SYMPTOMS. 

Among  the  main  muscular  symptoms  observed  in  Graves'  disease 
are:  tremor,  great  muscular  fatigue,  sudden  giving  way  of  the  knees, 
paresis,  and  paralysis. 

Tremor. — Alreadv  observed  by  Charcot,  in  1863,  tremor  was  carefully 
studied  later  by  Marie,  and  considered  by  him  as  one  of  the  cardinal 
svmptoms  of  Graves'  disease.  Tremor  is  not  always  noticeable  exter- 
nally and  patients  often  describe  their  own  consciousness  of  tremor  as 
an  "inward  trembling;"  in  marked  cases,  they  are,  so  to  speak,  in  con- 
tinuous vibration.  Tremor  may  be  localized  or  general.  It  may  be 
localized  to  the  upper  extremities  only,  being  then  much  more  marked 
in  the  hands  and  extended  fingers;  it  may  even  be  more  developed  in 
one  side  than  in  the  other,  while  in  rare  instances,  it  may  be,  or  may 
become  unilateral.  In  the  lower  extremities  it  is  best  seen  when  the 
legs  are  stretched  out.  In  rare  instances,  tremor  extends  all  over  the 
body.  It  may  involve  the  tongue,  too;  in  that  case  fine  fibrillary  con- 
tractions are  seen  when  the  patient  is  asked  to  protrude  his  tongue. 
The  tremor  may  be  observed  in  the  lips  when  tightly  closed.  When 
only  half-shut  the  eyelids  may  show  some  tremor  which  may  become 
more  accentuated  when  the  eyelids  are  more  tightly  closed;  this  is 
known  as  the  Rosenbach  symptom.  This  symptom,  however,  is  not 
pathognomonic  of  Graves'  disease  as  it  is  often  found  in  neurasthenia 
and  other  nervous  conditions. 

Tremor  is  perhaps  one  of  the  earliest  symptoms  found  in  Graves5 
disease.  It  may  be  present  for  months  before  the  disease  is  fully  devel- 
oped. It  is  best  perceived  while  the  patient  is  sitting  or  standing  with 
outstretched  arms,  and  it  becomes  less  marked  in  the  lying  posture. 
Tremor,  just  as  with  the  other  thyrotoxic  symptoms,  is  variable  in  in- 
tensity, and  may  disappear  for  a  certain  period  of  time  and  then  reappear 
again.  According  to  Sattler,  who  went  over  the  literature  of  the  sub- 
ject very  carefully,  tremor  is  present  in  9  per  cent,  of  all  the  cases  of 
Basedow's  disease. 

The  chief  characteristic  of  the  thyrotoxic  tremor  is  its  exceeding 
fineness.  The  oscillations  are  frequent  and  of  uniform  rhythm,  from 
7  to  10  per  second;  the  amplitude  of  these  oscillations  is  small.  Mu- 
rine tremor  seen  in  Graves'  disease  resembles  in  its  amplitude  of  excur- 


332  MUSCULAR  SYMPTOMS 

sion,  rhythm,  and  frequency  the  tremor  which  is  seen  in  normal  indi- 
viduals with  this  difference,  however,  that  in  normal  individuals  the 
tremor  is  so  scarcely  noticeable  to  the  naked  eye  that  it  requires  the 
graphometer  to  bring  it  out.  This  has  been  beautifully  shown  by 
Sattler.  The  tremor  seen  in  normal  individuals  after  great  shock, 
violent  psychic  emotion,  is  of  the  same  character  as  the  one  seen  in 
Graves'  disease. 

Tremor  is  not  pathognomonic  of  Graves'  disease  since  it  is  also 
found  in  various  nervous  diseases.  The  thyrotoxic  tremor  has  a  smaller 
amplitude  than  the  one  seen  in  paralysis  agitans,  but  is  faster.  It  is 
faster,  too,  than  the  senile  tremor.  It  resembles  the  tremor  seen  in 
hysteria,  in  traumatic  neurosis,  and  in  alcoholism.  Besides  tremor  there 
are  sometimes  observed  in  Graves'  disease  jerk)',  involuntary  move- 
ments, especially  of  the  head  and  extremities,  reminding  one  of  chorea. 

Great  Muscular  Fatigue. — Great  muscular  fatigue  is  a  frequent  accom- 
paniment of  Graves'  disease.  Spells  of  fatigue,  or  asthenic  crises,  of  very 
mild  type,  are  frequently  seen  in  normal  individuals.  How  often  do  we 
not  hear  normal  individuals  say,  "I  am  all  in,  today,"  or  "I  don't  feel 
up  to  the  mark!"  Yet,  there  is  no  apparent  cause  for  that  state.  I  do 
not  think  there  is  an  individual  who  is  so  normal,  so  well-balanced  as  to 
enjoy  uninterrupted  perfect  physical,  moral  and  intellectual  equilibrium. 
Everyone  has  his  ups  and  downs,  no  matter  how  mild  they  are.  These 
spells  of  lassitude  are,  as  a  rule,  purely  physical.  They  come  on  without 
any  apparent  cause;  last  probably  a  few  days  and  then  disappear  as 
they  came  without  any  apparent  reason  for  them.  These  asthenic  spells 
are  characterized  by  a  more  or  less  complete  reluctance  to  physical  effort, 
the  least  exertion  seems  to  tire  immensely.  Otherwise  the  individual 
is  all  right.  He  may  possibly  complain  of  some  intellectual  laziness,  or 
of  some  diminution  of  sexual  appetite,  but  that  is  all.  As  soon  as  the 
spell  is  over  the  individual  feels  all  right  again.  These  spells  may  recur 
from  two  to  three  times  a  year,  and  sometimes  more  frequently.  Changes 
in  the  weather  and  in  seasons  are  often  considered  as  a  cause  of  them, 
hence  the  terms  "spring  fever,"  etc. 

These  spells,  mild  and  capricious  in  nature,  are  likely  due  to  some 
rupture  in  the  equilibrium  existing  between  the  glands  of  internal  secre- 
tion. The  best  proof  for  this  is  that  the}7  are  successfully  combated 
with  extracts  from  the  endocrine  glands,  as  the  thyroid,  pituitary  body, 
adrenals,  ovarian  and  testicular  extracts. 

These  asthenic  spells  which  we  find  barely  sketched  in  normal  indi- 
viduals and  without  any  pathological  ground  for  them,  we  find  extremely 
marked  in  Basedow  patients.  They  may  reach  an  extreme  degree  of 
intensity  and  last  over  periods  of  months,  sometimes  of  years.  This 
sense  of  extreme  fatigue  is  not  relieved  by  rest  in  bed,  because  in  the 


TREMOR  333 

morning  the  patient  rises  as  tired,  if  not  more  tired  than  he  was  when 
he  went  to  bed.  The  weakness  involves  the  entire  musculature.  Meas- 
ured with  the  dynamometer,  the  muscular  strength  shows  considerable 
diminution.  In  some  instances  physical  effort  has  become  so  repugnant 
that  the  patient  lies  motionless  in  bed,  even  refusing  to  perform  the 
most  necessary  movements  necessitated  by  feeding,  etc. 

How  can  we  explain  this  muscular  hypotonus  r  \  erv  likelv,  through 
some  interference  with  the  function  of  the  suprarenal  bodies.  We  know 
that  their  cortical  cells,  the  spongiocytes,  are  entrusted  with  the  duty  of 
neutralizing  the  muscular  toxins,  and  that  the  medullary  cells,  the 
chromaffin  cells,  produce  adrenalin  whose  tonic  action  especially  upon 
the  circulatory  and  muscular  systems  is  well  known.  On  the  other 
hand,  wre  know,  too,  that  the  thyroid  secretion  is  antagonistic  to  that 
of  the  suprarenal  bodies.  In  hyperthyroidism  this  antagonistic  action 
will  be  pushed  to  the  maximum,  especially  if  the  case  is  complicated 
with  thymus  hyperplasia  since  we  know,  indeed,  that  the  thymus  is 
another  antagonist  of  the  adrenal  glands.  Most  likely  other  organs  of 
internal  secretion  intervene  also.  Consequently,  if  we  sum  up  all  these 
influences,  we  must  expect  a  marked  adrenal  insufficiency.  In  fact 
that  is  just  what  happens.  A  number  of  postmortems  of  cases  of 
Graves'  disease  have  shown  that  the  size  of  the  adrenal  glands  was 
materially  reduced. 

Sudden  Giving  Way  of  the  Knees. — One  symptom  which  is  quite  often 
seen  in  Graves'  disease  is  the  sudden  giving  wav  of  the  knees.  This 
occurs  without  any  warning,  without  any  vertigo;  the  patient  suddenly 
drops  as  if  his  legs  were  cut  away  from  under  him.  It  is  most  likelv  to 
occur  when  the  patient  is  going  downstairs,  or  when  he  is  in  a  hurry  to 
catch  a  car,  or  in  some  activity  of  that  kind.  The  patient  often  has 
difficulty  in  getting  up  without  aid;  sometimes  he  cannot  do  so  at  all. 

Once  in  a  while  the  muscular  hypotonus  becomes  so  marked  as  to 
cause  true  muscular  paresis  and  paralysis  as  is  shown  bv  the  paralysis 
of  the  frontal  muscle;  as  a  consequence  of  it  the  forehead  does  not 
wrinkle  but  remains  motionless. 

Muscular  Cramps.  Muscular  cramps  occur  once  m  a  while  in  con- 
junction with  Graves'  disease.  They  arc  mostly  localized  in  the  calf  <>t 
the  leg  and  occur  during  the  night.  Cramps  in  the  arms  and  hands. 
somewhat  tetamform  in  character,  have  been  observed  very   rarely. 

Tendinous  Reflexes.  In  the  majority  of  true  exophthalmic  goiters 
it  can  be  said  that  the  tendinous  reflexes  arc  rather  exaggerated.  1  hey 
may  be,  however,  normal,  diminished,  or  even  non-existent. 


CHAPTER   XXV. 

NERVOUS   AND   MENTAL   SYMPTOMS   IN   BASEDOW'S 

DISEASE. 

Broadly  speaking,  more  or  less  all  of  the  clinical  symptoms  seen  in 
Graves'  disease  are  of  nervous  origin,  because  they  are  the  results  of 
the  involvement  of  the  nervous  system  governing  the  vegetative  life. 
In  sens u  strictiori,  however,  there  are  symptoms  which  are  more  than 
others  directly  due  to  some  disturbances  of  the  nervous  system.  These 
are  the  ones  which  we  are  going  to  study  in  this  chapter. 

The  chief  nervous  characteristics  seen  in  Basedow's  disease  are: 
emotionality,  irritability,  restlessness,  and  instability.  More  severe  cere- 
bral disturbances  may  also  be  observed  such  as  obsessions,  impulsions, 
hallucinations,  and  mental  confusion.  True  insanity  may  even  be 
encountered. 

Basedow  patients  are,  above  all,  emotional.  The  slightest  cause  will 
throw  them  into  a  wild  state  of  excitement  which  goes  hand  in  hand 
with  an  exacerbation  of  their  physical  state.  As  Peter  has  said,  "Base- 
dow patients  can  be  compared  in  every  respect  to  normal  individuals 
subjected  to  great  excitement."  In  both  conditions  anxiety,  palpita- 
tion, tremor,  secretory  disturbances,  such  as  perspiration,  diarrhea,  and 
polyuria,  etc.,  are  present.  Some  Basedow  patients  are  afflicted  with  a 
pathological  sensitiveness;  they  laugh  and  cry  apparently  without  the 
slightest  cause.  Some  of  them  have  fits  of  religious  mysticism,  some 
others  show  abnormal  excitation  of  the  sexual  apparatus,  while  others 
live  in  a  state  of  constant  fear.  I  recall  a  patient  who  developed  a 
marked  mania  for  music.  Although  devoid  of  any  special  musical  gift, 
whenever  she  heard  music  she  would  plunge  herself  into  a  semicataleptic 
state,  recoiling  within  herself,  with  a  fixed  and  staring  look,  tense,  and 
vibrating.  One  would  have  thought  that  she  was  enjoying  a  paroxysm 
of  artistic  sensations.  Possibly  she  was,  yet  there  was  always  in  my 
mind  a  suspicion  that  a  great  deal  of  it  was  simply  affected.  This  fact 
should  not  diminish  at  all  the  interest  in  the  observation,  inasmuch  as 
simulation  and  deceit  are  among  the  features  of  certain  hysterical 
derangements.  I  recall  another  patient  who  developed  a  sudden  morbid 
passion  for  cards.  In  conclusion  it  may  be  said  that  the  emotionality 
in  Graves'  disease  is  nearly  always  exaggerated  and  consequently 
pathological. 

Some  thyrotoxic  patients  become  exceedingly  irritable.  They  may 
enter  into  the  most  paroxystic  fits  of  rage.    Trousseau  has  said  that  some 


XERVOUS  SYMPTOMS  IN  BASEDOW'S  DISEASE  335 

Basedow  patients  live  in  a  state  of  perpetual  anger.  Although  possibly 
of  quiet,  nice,  self-possessed  disposition  previous  to  the  outbreak  of 
the  disease,  these  patients  become  difficult  to  handle.  They  quarrel 
with  their  most  intimate  friends,  and  render  life  miserable  for  the  mem- 
bers of  their  families.  Their  love  for  their  own  relatives  becomes  less 
and  less  marked;  they  think  only  of  themselves  and  become  extremely 
and  peculiarly  egotistical.  They  require  the  most  constant  attention 
and  even  when  the  most  devoted  care  is  given  them  they  complain  of 
being  neglected.  Gradually  their  love  changes  into  hate.  This  frame 
of  mind  will  explain  why  a  great  number  of  these  patients  are  divorced 
or  separated  women,  and  why  some  of  them  are  simply  abandoned  by 
their  husbands.  Of  course  this  is  no  excuse  for  the  husband's  cowardly 
act,  but  may  explain  it  to  a  certain  extent.  Too  often,  I  am  sure, 
the  husband  does  not  realize  that  his  wife's  bad  temper  is  pathological, 
that  she  should  be  treated  as  a  sick  woman,  but  rather  takes  it  for 
granted  that  his  wife  has  an  infernal  disposition,  and  that  both  will  be 
better  off  separated. 

The  mental  condition  in  Basedow's  disease  is  most  restless  and 
unstable;  it  varies  with  the  degree  of  excitation  or  depression  in  which 
the  patient  finds  himself.  If  he  is  undergoing  a  period  of  excitation,  his 
intelligence  is  vivid  and  excessively  mobile.  The  patient  will  spend 
hours  in  thinking  and  scheming,  and  will  translate  his  exaggerated  men- 
tal activity  into  a  profuse  loquacity,  talking  about  everything  in  the 
most  superficial  way,  and  jumping  from  one  subject  to  another  with- 
out the  slightest  effort:  if  I  may  be  allowed  to  use  a  metaphor,  he  is 
suffering  from  a  veritable  "cerebral  diarrhea."  Usually  the  memory  is 
good.  With  this  exaggerated  mental  activity  there  goes  hand  in  hand 
an  increased  physical  activity.  The  Basedow  patient  is  exceedingly 
restless,  constantly  moving,  and  changing  position.  He  is  unable  to 
remain  seated  very  long  at  a  time,  but  goes  and  comes,  sits  and  rises, 
and  makes  hasty  movements — many  of  them  involuntary  and  without 
purpose.  The  patient  shows  considerable  ardor  in  the  accomplishment 
of  the  various  tasks  he  undertakes,  but  as  he  is  mentally  unstable,  he 
seldom  terminates  what  he  starts  out  to  do.  He  will  tackle  one  job  after 
another,  but  will  not  accomplish  much;  in  short,  he  shows  an  incoherent 
activity  without  any  definite  purpose. 

In  other  patients,  on  the  contrary,  we  find  mental  depression;  they 
cannot  concentrate  their  attention  upon  any  subject  without  the  great- 
est fatigue.  Their  memories  are  weak  and  untrue.  There  is  a  marked 
intellectual  laziness  which  prevents  them  from  pursuing  a  train  ot 
ideas.  At  the  same  time  there  exists  a  more  or  less  complete  physical 
apathy.  Since  their  mental  faculties  are  depressed  and  their  physical 
needs  are  reduced  in  the  same  proportion,  these  patients  will  lie  motion- 
less in  bed,  every  physical  effort  being  distasteful,  even  painful  to  them. 


336  NERVOUS  SYMPTOMS  IN  BASEDOW'S  DISEASE 

In  conclusion  we  may  repeat  what  we  said  in  the  beginning  of  this 
chapter:  the  nervous  and  mental  state  in  exophthalmic  goiter  is  charac- 
terized bv  emotionality,  irritability,  restlessness,  and  instability.  These 
pathological  features  are  subject  to  great  variations;  they  improve  as 
the  thyrotoxicosis  subsides  and,  vice  versa,  they  become  more  marked  as 
the  thyrotoxic  condition  gets  worse. 

In  the  late  stage  of  the  disease  these  psychic  disturbances  may 
acquire  a  more  serious  character. 

Not  so  infrequently  the  exophthalmic  goiter  will  terminate  by  an 
acute  delirium.  This  delirium  resembles  in  every  respect  the  one  seen 
after  intoxication  with  iodoform  and  in  postoperative  hyperthyroidism. 
In  all  three  conditions  the  patient  shows  an  extreme  agitation  and  is 
delirious;  he  does  not  recognize  his  attendants  any  longer,  nor  the 
members  of  his  family;  he  wants  to  get  rid  of  his  covers,  his  dressings, 
to  get  out  of  bed,  and  almost  invariably,  he  "wants  to  go  home."  Some- 
times it  takes  several  nurses  to  hold  him  in  bed.  He  talks  constantly 
in  a  more  or  less  incoherent  manner  about  those  things  which  are 
familiar  to  him,  especially  those  of  his  occupation  or  profession.  If  he 
is  a  farmer,  he  may  talk  about  pitching  hay;  if  he  is  a  lawyer,  he  may 
talk  about  defending  a  suit;  if  the  patient  is  a  housekeeper,  about  some 
feature  of  housekeeping.  This  delirium,  however,  is  not  systematized. 
It  is  usually  accompanied  by  hallucinations.  Then  the  patient  speaks 
to  people  whom  he  sees  in  his  delirium  dreams;  they  may  stand  beside 
him  or  on  his  bed;  they  may  be  at  the  threshold  of  the  room,  or  perhaps 
climbing  over  the  window.  Not  infrequently  one  will  gather  from  what 
the  patient  says  that  the  people  whom  he  sees  want  to  do  him  harm, 
that  they  want  to  kill  him. 

This  form  of  delirium  may  last  for  days  and  weeks,  and  usually 
terminates  in  death.  That  this  form  of  delirium  is  in  direct  etiological 
relation  to  thyrotoxicosis  there  can  be  no  doubt.  As  said  before,  it 
resembles  so  closely  the  one  seen  in  certain  forms  of  postoperative 
hyperthyroidism  that  its  etiology  must  be  the  same. 

That  hysteria  may  be  found  in  combination  with  Graves'  disease 
cannot  be  denied.  It  is  a  complication  seen  more  often  in  young  women 
than  in  men,  and  it  may  develop  later  as  a  complication  of  Graves' 
disease.  As  a  rule,  however,  when  hysteria  is  present,  it  has  existed 
before  Basedow's  disease  underwent  its  development.  That  hysteria  is 
an  entity  by  itself  is  shown  by  the  fact  that  it  does  not  follow  the  course 
of  Graves'  disease,  improving  when  the  latter  improves,  and  getting 
worse  when  the  other  undergoes  exacerbations.  The  hysterical  symp- 
toms may  follow  their  course,  getting  worse  while  the  thyrotoxic 
symptoms  gradually  disappear. 

It  would  be  a  mistake,  however,  to  believe  that  the  majority  of 
Basedow  patients  are  hysterical;  this  is  not  so.     In  my  own  experience, 


XERVOUS  SYMPTOMS  IN  BASEDOW'S  DISEASE  337 

I  would  say  that  the  majority  of  patients  do  not  show  the  characteristic 
mental  accompaniments  of  hysteria.  As  Thomson  says,  "They  look 
their  physician  straight  in  the  face,  and  show  no  response  to  suggestions. 
They  deny  the  symptoms  which  they  do  not  have,  and  remain  consis- 
tent in  their  description  of  the  symptoms  which  they  have,  with  no 
variation  in  their  story  for  months,  while  they  are  always  ready  to 
acknowledge  any  improvement  in  their  symptoms  when   thev  occur." 

Neurasthenia  sometimes  occurs  as  a  complication  of  Graves'  disease; 
it  is  more  frequent  in  men  than  in  women.  Like  hysteria,  it  is  not  in 
direct  relation  to  thyrotoxicosis,  but  seems  to  be  a  nervous  disturbance 
per  se. 

There  are,  however,  a  number  of  psychoses  which  occur  in  conjunc- 
tion with  Graves'  disease  whose  etiological  relation  is  still  an  open 
question  for  discussion.  I  have  in  mind  those  transitory  obsessions  and 
impulsions  which  are  sometimes  seen  in  Basedow's  disease.  In  1871 
Solbrig  reported  the  case  of  a  woman,  who,  although  deeply  loving  her 
children,  wanted  to  kill  them.  I  have  seen  a  similar  case.  It  was  that 
of  a  woman  who  felt  at  times  an  irresistible  impulse  to  kill  her  child. 
A  patient  of  Raymond  and  Seneux  was  afraid  to  cross  a  large  public 
square  because  she  thought  that  she  was  bound  to  be  run  over  by  a 
wagon.  Another  patient  thought  that  she  was  going  to  die,  that  her 
heart  was  going  to  burst,  or  that  something  was  going  to  fall  upon  her 
and  crush  her.  Some  patients  have  a  tendency  to  suicide,  and  a  patient 
of  Plaignard  constantly  saw  herself  hanging  to  a  window.  All  these 
obsessions,  impulsions,  and  phobia  have  the  peculiarity  of  being  irre- 
sistible, or  at  least,  of  being  filled  with  the  utmost  anxiety.  The  obses- 
sion is  sometimes  so  intense  that  on  the  spur  of  it  the  patient  will  occa- 
sionally do  the  most  extravagant  things,  and  the  most  cruel  thing  of  all 
is  that  he  knows  that  his  impulses  are  wrong,  so  that  for  a  long  time  he 
will  fight  against  them;  hence  the  great  moral  and  mental  suffering 
which  terminates  only  when  the  impulsive  act,  no  matter  how  extrava- 
gant or  immoral,  has  been  accomplished.  Although  he  knows  that  he 
acted  wrongly,  nevertheless,  he  feels  a  sense  of  relief  and  satisfaction, 
temporary  at  least,  when  the  act  has  terminated  the  crisis. 

Exophthalmic  goiter  may  occur  as  a  complication  in  a  variety  of 
psychoses  such  as  in  pseudosystematized  delirium  of  degenerates,  in 
mania,  in  melancholia,  in  maniacal  states,  in  depressive  melancholia, 
in  delirium  acutum,  in  paranoia,  etc.  Vice  versa,  psychoses  may  follow 
after  Graves'  disease  has  long  been  fully  developed.  Psychoses  may 
occur  at  any  period  of  the  development  of  Graves'  disease.  Sometimes 
only  after  the  thyrotoxic  complex  has  subsided  entirely  do  we  see  the 
development  of  psychoses.  On  the  other  hand,  the  goiter  may  appear 
years  after  the  patient  has  had  psychic  disturbances  and  which  have 
long  since  subsided. 
22 


338  NERVOUS  SYMPTOMS  IN  BASEDOW'S  DISEASE 

We  have,  consequently,  the  right  to  ask  ourselves  the  following 
question:  Is  there  a  true  thyrotoxic  insanity,  or  are  the  psychoses  found 
in  conjunction  with  Graves'  disease  purely  accidental?  From  all  the 
well-authenticated  cases  reported  in  the  literature  which  I  have  been 
able  to  lay  my  hand  upon,  it  seems  to  me  that  we  cannot  consider  these 
psychoses  as  of  thyrotoxic  origin.  They  are  only  associated  nervous 
disturbances,  grafted  upon  a  predisposed  terrain.  Here,  too,  we  find 
the  same  ladened  heredity,  and  the  same  psychic  as  well  as  physical 
stigmata  found  in  the  same  psychoses  complicated  with  Basedow's  dis- 
ease. That,  however,  Graves'  disease  supervening  in  such  predisposed 
and  unstable  terrain  is  bound  to  favor  the  eclosion  of  psychoses  is  a 
fact  which  every  one  will  readily  admit.  The  reverse  is  true,  too;  thyro- 
toxicosis will  evolve  more  easily  and  more  fully  in  individuals  whose 
nervous  system  is  already  in  an  unstable  equilibrium.  When  I  see 
certain  young,  nervous,  irritable  and  unstable  individuals,  I  cannot  help 
but  look  upon  them  as  future  candidates  for  Graves'  disease. 

Chorea  and  choreiform  conditions  are  sometimes  seen  in  conjunction 
with  Graves'  disease.  I,  myself,  have  met  with  that  combination  two 
or  three  times.  It  occurs  nearly  always  in  young  girls  and  children. 
There  is  no  definite  relation  between  the  two  conditions  as  to  their 
onset;  chorea  may  develop  first,  and  then  the  exophthalmic  goiter,  or 
vice  versa,  or  the  two  conditions  may  develop  at  the  same  time,  or  one 
of  them  may  regress  while  the  other  remains  progressive.  As  a  rule, 
however,  the  improvement  of  one  involves  the  betterment  of  the  other. 
Although  their  association  is  purely  accidental,  there  appears  to  be  in 
certain  instances  an  etiological  relation. 

Heredity  of  Graves'  Disease. — That  Graves'  disease  may  be  heredi- 
tary is  shown  by  a  number  of  examples.  Osterreicher  reported  the  case 
of  an  hysterical  woman  who  had  ten  children,  six  girls  and  four  boys. 
Eight  of  these  children  developed  Graves'  disease.  One  of  the  daughters 
married  and  had  four  children;  three  of  her  daughters  developed  exoph- 
thalmic goiter  and  the  fourth  was  hysterical.  Cantilena  reported  the 
case  of  an  hysterical  woman  having  two  children,  one  son  and  one  daugh- 
ter; both  had  exophthalmic  goiter.  The  daughter  herself  had  three 
girls,  two  of  whom  developed  exophthalmic  goiter.  Cheadle  saw  four 
cases  of  exophthalmic  goiter  in  the  same  family.  Thyssen  reported  a 
case  of  a  mother  and  daughter  having  exophthalmic  goiter.  Solbng  and 
Kronthal  also  reported  a  case  of  mother  and  child  having  exophthalmic 
goiter.  Dejenne  saw  a  family  in  which  exophthalmic  goiter  was  heredi- 
tary during  four  generations.  I  have  seen  three  sisters  afflicted  with 
exophthalmic  goiter;  in  another  instance  a  mother  and  her  daughter 
both  had  exophthalmic  goiter.  Similar  cases  are  not  so  rare.  It  is  not 
so  infrequent  to  see  Graves'  disease  develop  in  patients  whose  nervous 
heredity  is  heavy. 


CHAPTER   XXVI. 
DIGESTIVE   DISTURBANCES. 

Digestive  disturbances  are  very  frequent  in  Graves'  disease,  and 
their  importance  is  not  to  be  belittled,  because  they  will  often  so  inter- 
fere with  nutrition  that  life  is  endangered.  None  of  the  symptoms  seen 
in  Graves'  disease  seems  to  tell  upon  the  general  condition  of  the  patient 
so  much  and  so  quickly  as  gastro-intestinal  disturbances.  In  a  very 
short  time  the  patient  will  melt  away,  and  in  a  few  weeks  may  be  dead. 
We  have  all  seen  these  fulminating  forms  of  thyrotoxic  troubles  which 
in  less  than  six  or  ten  weeks  have  brought  a  Basedow  patient,  whose 
general  condition  at  the  onset  was  otherwise  good,  to  his  death. 

The  first  fact  to  note  is,  that  these  symptoms  develop  usually  when 
the  disease  is  in  its  incipiency.  A  number  of  times  they  will  be  found  in 
the  history  of  the  patient  so  long  before  any  of  the  thyrotoxic  symptoms 
have  been  clearly  established,  that  we  may  say  that  they  are  often  the 
forerunner  of  the  disease.  This  is  especially  true  for  diarrhea;  hence 
the  necessity  of  always  bearing  in  mind  the  possibility  of  Basedow  in 
cases  where  diarrhea  sets  in  without  apparent  cause,  remains  persistent 
for  a  while  and  then  subsides. 

The  other  fact  is  that  digestive  disturbances  are  distinctly  specific, 
and  manifestly  unlike  any  other  affections  of  the  gastro-intestinal  tract. 
In  their  mode  of  appearance,  in  their  pathological  manifestations,  and 
in  their  way  of  subsiding  they  are  always  the  same.  They  usually  occur 
without  any  apparent  cause  and  subside  the  same  way.  They  sometimes 
appear  to  follow  a  cycle.  With  their  paroxysmal  character  and  with 
their  peculiar  way  of  appearing  and  subsiding,  they  remind  one  of 
tabetic  crises.  Never  at  any  stage  of  their  development,  may  it  be  at 
the  beginning  or  the  end,  do  they  present  the  inflammatory,  exudative, 
or  ulcerative  characters  seen  in  other  pathological  conditions  of  the 
gastro-intestinal  tract. 

Finally,  they  are  most  uncontrollable  and  stubbornly  resist  any  form 
of  medical  treatment,  no  matter  at  what  stage  of  their  development  it 
may  be  instituted.  That  there  is  a  close  relation  between  the  disturb- 
ances of  the  gastro-intestinal  tract  and  the  other  thyrotoxic  symptoms 
is  shown  by  the  fact  that  the  course  of  the  latter  goes  hand  m  hand  with 
the  improvement  or  exacerbation  of  the  former.  One  thing  is  certain: 
no  improvement  in  the  disease  can  be  expected  so  long  as  the  gastro- 


340  DIGESTIVE  DISTURBANCES 

intestinal  symptoms  have  not  subsided.  On  the  other  hand,  when  once 
they  have  retroceded  entirely,  it  is  remarkable  to  see  how  quickly  a 
patient  will  rally  and  put  on  flesh,  even  when  his  condition  was  such  as 
to  appear  hopeless. 

Another  distinctive  feature  of  these  gastro-intestinal  disturbances  is 
the  acetone  breath  which  one  will  so  often  notice  while  near  the  patient, 
or  even  upon  entering  the  room.     It  is  due  to  acidosis. 

Let  us  take  these  gastro-intestinal  symptoms  separately  and  study 
them. 

Appetite. — Loss  of  appetite  is  very  common  and  one  of  the  early 
symptoms.  It  may  be  so  marked  as  to  lead  the  patient  into  a  state  of 
complete  anorexia.  I  have  seen  fatal  cases  which  for  weeks  showed  an 
absolute  repulsion  toward  food  of  any  sort.  In  these  cases  if  anorexia  is 
complicated  with  gastric  intolerance,  if  one  succeeds  in  getting  some 
food  into  the  patient's  stomach,  that  nourishment  comes  up  again  as 
quickly  as  it  went  down.  In  some  instances  loss  of  appetite  alternates 
with  spells  of  hunger.  In  other  conditions  the  patient  may  suffer  from 
bulimia;  the  appetite  is  then  ravenous  and  never  satisfied  no  matter 
how  much  food  the  patient  takes.  Bulimia  often  becomes  intense  dur- 
ing the  night.  It  may  even  exist  despite  the  most  intense  vomiting, 
diarrhea,  and  loss  of  flesh. 

Nausea. — A  very  common  thyrotoxic  disturbance  is  nausea.  It  is 
a  very  persistent  and  very  annoying  symptom  which  may  last  for  weeks, 
months,  or  even  years,  with  or  without  periods  of  remission.  It  is 
usually  more  marked  after  eating,  but  may  have  no  relation  whatsoever 
to  food,  occurring  as  often  with  empty  stomach  as  it  does  after  meals. 
Nausea  is  always  worse  in  the  morning;  it  rarely  leads  to  vomiting. 

Gastric  Flatulence. — This  is  another  symptom  which  often  goes  with 
the  gastro-intestinal  disturbances  in  Graves'  disease;  it  has  a  most  per- 
sistent character.  The  patients  attempt  to  relieve  themselves  by  fre- 
quent eructations  which  have  none  of  the  acid  or  acrid  characteristics 
seen  in  other  gastric  disturbances.  It  seems  to  be  mostly  air  which 
they  eructate.  This  would  lead  to  the  belief  that  some  of  the  patients 
are  aerophages  or  air-suckers. 

Vomiting. — In  more  serious  gastric  disturbances  vomiting  is  always 
present.  It  may  be  so  marked  as  to  endanger  the  life  of  the  patient. 
It  occurs  with  empty  stomach  as  well  as  after  taking  food.  When  not 
too  severe,  it  may  take  place  only  four  or  five  times  a  day,  while  in  severe 
conditions  it  may  occur  as  often  as  ten  to  fifteen  times  a  day.  The  vom- 
itus  may  be  watery,  slimy,  or  colored  with  bile;  blood  is  very  seldom 
found,  but  if  it  is,  it  is  only  under  the  form  of  some  bloody  streaks  due 
very  likely  to  injury  of  the  mucous  membrane  of  the  stomach  or  esoph- 
agus through  the  efforts  made  in  vomiting.    As  shown  by  repeated  fluoro- 


DIARRHEA  341 

scopic  examinations,  the  stomach  is  in  a  state  of  more  or  less  constant 
spasticity. 

Nothing  definite  is  known  about  the  gastric  chemistry  in  hyper- 
thyroidism and  especially  during  the  gastro-intestinal  disturbances.  As 
a  rule  there  seems  to  be  either  anachlorhydna  and  apepsia,  or  hypo- 
chlorhydria  and  hypopepsia.  In  some  instances,  however,  there  is 
undoubtedly  hyperchlorhydria. 

Diarrhea. — Diarrhea  is  among  the  most  important  digestive  disturb- 
ances in  Graves'  disease.  Its  running  down  effect  upon  the  patient  is 
possibly  more  marked  than  that  of  vomiting.  Apparently  without  any 
precise  cause  and  usually  in  no  relation  to  the  taking  of  food,  the  patient 
will  have  a  number  of  stools  which  may  vary  from  4  to  30  in  twenty- 
four  hours.  These  stools  are  watery,  yellowish  or  gray  in  color,  and 
often  contain  bile  products.  It  is  interesting  to  note  that  in  certain 
cases  the  stools  contain  a  great  quantity  of  undigested  fat.  As  a  rule 
the  discharges  are  not  offensive  and  do  not  contain  blood,  mucus,  or 
pus.  They  are  neither  preceded  nor  followed  by  pain,  although  the  patient 
may  complain  of  a  diffuse  distress  throughout  the  abdomen  and  of 
some  flatulence.  Like  vomiting  they  show  morning  exacerbations.  No 
medical  treatment  seems  to  have  any  hold  upon  them.  Diarrhea  may 
alternate  with  spells  of  constipation.  Often,  however,  as  soon  as  diarrhea 
has  subsided,  the  intestinal  tract  resumes  its  normal  function,  just  as 
if  nothing  had  ever  happened.  If  diarrhea  is  moderate  and  unaccom- 
panied by  vomiting,  and  if  the  appetite  remains  fair,  its  effect  upon  the 
patient  will  soon  pass  unnoticed.  If,  however,  diarrhea  becomes  severe 
and  is  at  the  same  time  complicated  with  vomiting,  the  resistance  of  the 
patient  will  be  put  to  a  severe  test. 

In  a  few  cases  of  very  severe  thyrotoxicosis,  icterus  may  be  observed. 
This  icterus  is  rare,  although  it  is  not  uncommon  to  observe  a  yellowish 
tint  of  the  sclerotica  in  severe  thyrotoxic  gastro-intestinal  disturbances. 
The  prognosis  of  this  icterus  is  always  bad.  This  icterus  is  not  due  to 
any  obstacle  in  the  bile  ducts,  but  is  of  toxic  origin. 

I  think  we  are  within  our  rights  when  we  say  that  these  gastro- 
intestinal symptoms  are  of  vagal  and  sympathetic  origin,  secondary  to 
some  toxic  influence  of  the  thyroid  secretion  upon  the  s\  mpathetico- 
vagal  system. 


CHAPTER  XXVII. 
GENITAL   DISTURBANCES. 

Menstrual  disturbances  are  quite  frequently  seen  in  conjunction 
with  Basedow's  disease.  Although  once  in  a  while  one  may  meet  with  a 
case  in  which  menstruation  is  prolonged  and  profuse,  as  a  rule,  how- 
ever, the  opposite  is  true  in  the  great  majority  of  cases.  In  these  men- 
struation becomes  irregular,  scant,  and  often  stops  altogether  for 
periods  which  may  last  months  or  even  years.  In  some  instances 
menstruation  ceases  abruptly  long  before  any  true  symptoms  of  the 
disease  show  up.  There  is  then  a  premature  menopause  which  may 
remain  permanent,  no  matter  if  it  does  occur  a  number  of  years  before 
the  natural  time  for  menopause  has  come.  I  have  seen  thyrotoxic  cases 
in  which  premature  menopause  occurred  at  twenty-eight,  twenty-nine, 
or  thirty  years  of  age,  and  which  remained  permanent  after  that.  More 
frequently,  however,  menstrual  disturbances  develop  gradually  and  in 
direct  proportion  to  the  severity  of  the  disease.  As  soon,  however,  as  the 
thyrotoxic  condition  begins  to  improve,  menstruation  gradually  returns 
to  its  normal  condition.  The  most  hopeful  sign  in  Graves'  disease  is  the 
return  of  menstruation. 

With  the  menstrual  disturbances,  there  ceases,  or  at  least,  diminishes 
to  a  great  extent,  the  sexual  appetite;  the  entire  genital  apparatus 
undergoes  atrophy  and  sclerosis;  the  uterus,  tubes,  and  ovaries  become 
small.     If  the  patient  is  a  man,  the  testicles  undergo  atrophy. 

In  conclusion  we  may  say  that  in  Graves'  disease  the  entire  genital 
apparatus  is  in  a  state  of  hypofunction. 

Gynecological  lesions,  such  as  inflammations,  tumors,  and  mal- 
position of  the  genital  organs,  are  sometimes  found  in  conjunction  with 
Graves'  disease.  In  some  instances  the  surgical  treatment  of  these 
gynecological  lesions  resulted  in  the  absolute  cure  of  the  thyrotoxic 
symptoms. 


CHAPTER   XXVIII. 
RESPIRATORY   DISTURBANCES. 

In  Graves'  disease  respiration  certainly  does  not  follow  the  same 
rhythm  seen  in  normal  individuals.  It  is  rapid,  superficial,  and  irregular 
in  character;  it  alternates  with  periods  of  rest  which,  in  turn  are  irregu- 
larly interrupted  by  one  or  two  deep  respirations  which  have  more  the 
.character  of  a  sigh:  there  exists  a  true  respiratory  arrhythmia.  The 
number  of  respirations  may  attain  the  double. of  the  normal  number. 
Hofbauer,  of  Vienna,  has  shown  that  the  respiratory  curves  in  Graves' 
disease  have  a  decided  type  of  their  own.  The  amplitude  of  their  excur- 
sion is  shorter  than  those  seen  in  normal,  and  other  pathological  condi- 
tions; furthermore,  inspiration  and  expiration  are  exactly  equal  in 
length;  finally,  these  respiratory  curves  are  irregular.  Hofbauer  claims 
that  this  type  of  curve  is  characteristic  for  Graves'  disease,  and  that  it 
is  seen,  not  only  in  patients  complaining  of  shortness  of  breath,  but  in 
the  ones  who  apparently  are  not  conscious  of  any  respiratory  trouble. 
Naturally,  since  short  and  superficial  respiration  will  have  as  a  corollary 
a  diminished  amplitude  of  the  thoracic  excursions,  and  since  inspiration 
and  expiration  are  of  equal  length,  it  follows  that  the  excursions  of  the 
thorax  during  inspiration  and  expiration  will  be  reduced  in  the  same 
proportion.  This  can  be  easily  demonstrated  with  a  special  apparatus 
for  thoracic  measurements,  as  was  shown  by  Louise  Fiske  Bryson  in 
1889.    This  symptom  has  since  then  been  known  as  the  Bryson  symptom. 

Shortness  of  Breath. — Shortness  of  breath  is  often  complained  of  by 
Basedow  patients.  It  may  be  constant  or  may  come  on  by  spells.  It 
may  be  present  with  or  without  physical  exercise,  but  always  becomes 
more  marked  when  the  patient  does  some  exertion  or  undergoes  some 
psychic  excitement.  This  shortness  of  breath  in  the  great  majority  of 
cases  is  not  in  relation  at  all  to  the  volume  of  the  thyroid.  This  might 
have  been  foreseen,  as  we  all  know  that  mechanical  disturbances  of  the 
trachea  do  not  cause  a  rapid  and  superficial  respiration,  but  on  the 
contrary,  that  under  such  conditions  respiration  is  slower  and  deeper. 
Might  not  this  shortness  of  breath  be  of  cardiac  ongm:  It  is  true, 
indeed,  that  in  certain  advanced  cases  of  hyperthyroidism  we  have 
marked  cardiac  disturbances  due  to  vascular  and  valvular  insufficiency. 
Under  such  conditions  we  shall  have  to  admit  that  shortness  of  breath 
will  be  mostly  due  to  cardiac  troubles,  but  there  again  the  respiratory 


344  RESPIRATORY  DISTURBANCES 

disturbances  have  a  decided  character  of  their  own  with  which  every 
one  is  familiar.  Since  shortness  of  breath  is  observed  from  the  early 
beginning  of  the  disease  at  the  time  when  the  cardiac  muscle  is  still 
strong  and  its  valves  are  still  continent,  we  shall  have  to  find  something 
else  than  the  heart  to  explain  it.  As  we  have  seen,  the  cause  of  this 
shortness  of  breath  is  the  disturbed  rhythm  of  the  respiratory  apparatus 
itself.  Respiration  is  superficial;  the  amplitude  of  the  thorax  is  dim- 
inished materially,  and  consequently,  the  intake  of  air  is  ipso  facto 
reduced.  These  disturbances  will  naturally  lead  to  insufficient  oxygen- 
ation of  the  blood  and  will  contribute  toward  increasing  the  already 
disturbed  metabolism.  But  the  true  primary  cause  is  most  certainly  in 
the  direct  influence  of  the  thyrotoxin  upon  the  respiratory  centers.  In 
advanced  cases  degeneration  of  the  respiratory  musculature,  especially 
of  the  diaphragm,  as  has  been  shown  by  Askanazy,  might  be  considered 
as  an  adjuvant  factor. 

Coughing. — A  symptom  which  when  present  is  persistent  and  annoying 
is  coughing.  The  thyrotoxic  cough  is  dry  and  not  accompanied  by 
expectoration;  no  pulmonary  lesions  are  at  the  bottom  of  it.  It  is  often 
exaggerated  by  the  recumbent  position,  and  becomes  consequently 
annoying  to  the  patient  because  it  prevents  him  from  sleeping.  In  the 
great  majority  of  cases  this  coughing  is  not  caused  at  all  by  the  pressure 
of  the  goiter  upon  the  trachea,  but  according  to  Sattler,  it  is  caused  by 
an  exaggerated  sensibility  of  the  mucous  membrane  of  the  entire  respira- 
tory apparatus.  Under  such  conditions  the  irritant  which  in  ordinary 
conditions  would  pass  unnoticed  is  sufficient  to  produce  a  reflex  cough. 
It  must  not  be  forgotten  that  many  of  these  coughing  spells  are  of 
hysterical  origin. 

Hoarseness. — Hoarseness,  without  any  definite  pathological  reason,  is 
seldom  seen.  Weakness  of  the  voice,  however,  is  much  more  frequent, 
and  may  sometimes  lead  to  aphonia.  The  latter  symptom  is  not  in 
relation  to  the  size  or  to  the  position  of  the  goiter.  Patients  often 
complain  at  the  same  time  of  a  sense  of  constriction  in  the  throat,  and 
sometimes  accompanied  by  pain.  These  manifestations  are  nearly 
always  of  hysterical  origin. 


CHAPTER  XXIX. 
SENSORY   DISTURBANCES  AND   INSOMNIA. 

A  sense  of  throbbing  and  tinnitus  in  the  ears  is  sometimes  com- 
plained of  by  Basedow  patients.  Rarely  there  is  a  disturbance  in  the 
sense  of  smell.  As  said  previously,  patients  complain  of  pain  in  the 
eyes,  of  flashes  of  light,  and  of  dark  and  bright-colored  spectra. 

Pains. — Pains  are  among  the  most  common  complaints  of  Basedow 
patients.  These  pains  are  exceedingly  variable  as  to  their  seat  and  nature. 
They  may  implicate  such  various  parts  of  the  body  as  the  tips  of  the 
fingers  or  toes,  the  heels,  the  palms  of  the  hands,  the  upper  and  lower 
extremities,  and  the  joints,  such  as  the  knees,  wrists,  and  ankles.  Often 
these  pains  are  purely  muscular.  The  most  common  site  is  in  the  muscles 
of  the  neck,  especially  the  sternocleidomastoid  muscles.  These  pains 
differ  from  rheumatic  pains  since  they  are  extremely  shifting  in  charac- 
ter. The\'  are  not  painful  to  firm  palpation,  do  not  show  anv  swelling 
and  are  not  materially  affected  by  changes  in  the  weather.  The)'  may  be 
distinguished,  too,  from  peripheral  neuritis  by  their  transient  character. 

Headaches. — Headaches  are  among  the  most  frequent  sensory  disturb- 
ances observed  in  Graves'  disease.  Intermittent  in  character,  they  may  be 
in  some  patients  of  almost  daily  occurrence.  The)'  are  of  the  migrainous 
type.  Sometimes  the)'  are  periodical,  occurring,  for  instance,  at  the 
menstrual  periods.  In  the  majority  of  cases  they  are  characterized  by 
the  patient  as  "dull"  headaches;  sometimes  they  take  the  form  of 
violent  headaches.  They  are  mostly  localized  in  the  occipital,  the  fron- 
tal, or  the  temporal  regions,  and  are  most  frequently  complained  of  in 
the  morning.  They  are  seldom  accompanied  by  nausea  or  vomiting, 
and  differ  from  typical  attacks  of  migrain  in  not  coming  on  in  severe 
paroxysms,  and  in  not  leading  to  vomiting. 

It  is  self-evident  that  all  patients  suffering  from  headaches  are  not 
thyrotoxic  patients.  Since  headaches  occur  with  predilection  in  neuro- 
pathic individuals,  it  is  fair  to  admit  that  Graves'  disease  will  only 
exaggerate  this  neuropathic  tendency,  and,  consequently  will  increase 
the  chances  for  headache;  hence  the  frequency  of  the  symptom.  We 
might  even  go  further  and  admit  in  certain  conditions  the  existence  of  a 
true  thyrotoxic  headache,  dull  in  nature,  mostly  localized  in  the  occipital 
region,  and  subject  to  morning  exacerbations.  Often,  too,  headache  is 
only  a  symptom  of  acidosis  which  frequently  accompanies  thyrotoxicosis. 


346  SENSORY  DISTURBANCES  AND  INSOMNIA 

Vertigo. — Occasionally  vertigo  is  complained  of  by  the  patients.  It 
is  often  associated  with  aural  disturbances  and  is  more  pronounced  in 
patients  complaining  of  throbbing  and  tinnitus  of  the  ears. 

Tingling  and  Numbness. — Tingling  and  numbness  of  the  upper  and 
lower  extremities  is  sometimes  another  complaint;  it  is  more  frequently 
observed  in  the  lower  limbs. 

INSOMNIA. 

Another  of  the  frequent  complaints  of  Basedow's  disease  is  insomnia. 
From  a  light  sleep  often  interrupted  by  periods  of  wakefulness,  up  to  a 
more  or  less  complete  insomnia,  all  degrees  are  seen.  The  patient  may 
enjoy  a  few  hours  sleep  in  the  early  part  of  the  night,  but  after  mid- 
night insomnia  becomes  stubborn.  Very  often  sleep  is  disturbed  by 
dreams,  more  or  less  unpleasant,  and  which  sometimes  take  the  form  of 
frightful  nightmares. 


CHAPTER   XXX. 
CUTANEOUS   SYMPTOMS. 

Sensation  of  Heat. — Vasomotor)'  disturbances  are  quite  frequent  in 
Graves'  disease;  the)'  manifest  themselves  commonly  by  an  exaggerated 
sensation  of  heat.  Basedow  patients  are  always  warm,  in  fact,  too  warm, 
although  their  bodily  temperature  is  normal.  When  other  people  feel 
comfortably  cool  or,  in  fact,  even  cold,  Basedow  patients  will  still  complain 
of  being  too  warm;  they  seek  drafts.  During  the  coldest  weather  the)' 
feel  comfortable  only  if  the  windows  and  doors  are  open.  They  wear  only 
thin  clothing,  far  too  thin  for  a  normal  individual  to  be  comfortable  in. 
The  winter  is  their  best  season,  while  in  summer  they  always  feel 
prostrated. 

Basedow  patients  often  complain  of  hot  flashes;  the)'  flush  easily 
and  have  red  cheeks;  the  least  physical  or  psychical  excitation  is  suffi- 
cient to  cause  a  marked  congestion  of  the  face  and  sometimes  of  the 
entire  body. 

Dermographism. — Dermographism  is  often  found  in  Graves'  disease. 
It  takes  its  origin,  too,  in  a  disturbed  vasomotor)'  function.  It  may  be 
obtained  by  scratching  the  skin  once  with  a  pencil  or  the  finger.  Two 
or  three  seconds  after  the  scratching  has  been  done,  a  red  line,  more  or  less 
intense,  appears  following  the  direction  of  the  scratching,  and  which  lasts 
quite  a  long  time  and  then  fades  away.  Not  so  infrequently  instead  of 
being  red,  the  line  is  white;  it  becomes  red  only  a  little  while  after.  In 
other  instances  the  white  line  is  surrounded  on  either  side  by  a  streak 
of  redness. 

Hyperhydrosis. — As  a  rule  Basedow  patients  suffer  a  great  deal  from 
hyperhydrosis.  They  sweat  continuously  and  profusely,  with  or  without 
any  physical  exercise,  and  very  often  at  night  as  well  as  in  the  daytime. 
These  sweatings,  like  the  other  thyrotoxic  symptoms,  are  subject  to  great 
variations,  being  more  marked  at  times  than  at  others.  As  a  rule  the 
sweat  is  odorless;  however,  in  rare  cases,  a  very  offensive  odor  has  been 
observed.  On  account  of  the  constant  moisture  of  the  skin  it  will  be 
easily  understood,  as  \  igouroux  has  shown,  why  the  skin  of  Basedow 
patients  offers  less  resistance  to  the  electrical  current  than  the  skin  of 
normal  individuals. 

Itching  of  the  Skin.  Not  very  frequent,  but  when  present  an  annoying 
symptom,  is  itching  of  the  skin.     It  may  be  accompanied  by  some  skin 


348  CUTANEOUS  SYMPTOMS 

eruption,  but  may  be  present,  too,  without  any  visible  involvement  of 
the  skin.  It  may  be  exceedingly  intense,  may  last  night  and  day,  and 
usually  follows  the  up-and-down  curves  of  the  disease,  improving  when 
Graves'  disease  subsides,  and  getting  worse  when  the  disease  undergoes 
exacerbations.  This,  however,  is  not  always  true.  I  have  had  recently 
under  observation  a  patient  whose  thyrotoxic  symptoms  have  almost 
entirely  subsided,  except  exophthalmos  and  itching.  Scratching  neither 
relieves  nor  aggravates  this  itching. 

Urticaria. —  Basedow  patients  are  apt  to  have  skin  eruptions.  The 
most  frequently  seen  is  urticaria,  which  in  some  cases  may  be  remarkably 
transient  in  character.  I  remember  a  case  in  which  urticaria  was  so  fuga- 
cious that  it  would  disappear  entirely  in  the  time  necessary  for  the  patient 
to  go  from  home  to  the  doctor's  office.  This,  however,  is  not  frequent, 
and  although  very  changeable  in  character,  it  may  nevertheless  last  for 
long  periods  of  time. 

Falling  of  the  Hair. — The  hair  becomes  dry,  brittle,  and  falls  out. 
The  same  is  true  of  the  nails  of  the  fingers  and  toes.  This  occurs  in  the 
early  beginning  of  the  disease  and  retrocedes  as  soon  as  the  condition 
of  the  patient  improves.  It  may  involve  not  only  the  hair  of  the  head, 
but  also  that  of  the  beard,  and  that  over  the  different  parts  of  the  body 
such  as  the  arms,  the  thorax,  and  the  axillary  space;  the  eyebrows  and 
eyelashes  may  even  fall  out.  In  all  respects  this  falling  resembles  the 
loss  of  hair  after  prolonged  fevers  such  as  typhoid,  and  as  they  do, 
likewise  recognizes  a  toxic  origin. 

Brown  Pigmentation  of  the  Skin,  which  may  sometimes  take  the 
bronzing  tint  seen  in  Addison's  disease  is  not  so  seldom  observed  in 
Graves'  disease.  It  may  involve  the  entire  body,  but  is  more  marked 
in  the  exposed  regions  such  as  the  face,  the  neck,  the  thorax  and  arms. 
Sometimes,  instead  of  being  diffusely  distributed,  it  is  localized  in  patches, 
and  in  that  case  is  more  marked  in  the  bend  of  the  elbows,  of  the  wrist, 
knees,  etc.  When  present,  it  is  always  more  marked  and  appears  first 
around  the  eyelids,  as  has  been  shown  in  the  chapter  on  Ocular  Symptoms. 

Circumscribed  edema  is  sometimes  observed;  its  site  of  predilection 
is  in  the  eyelids;  this  edema  sometimes  has  a  very  transient  character. 
It  is,  too,  of  nervous  origin. 


CHAPTER    XXXI. 
BLOOD   CHANGES   IN   BASEDOW'S    DISEASE. 

Although  Micsowicz  and  Ciuffini,  in  1904,  found  a  lymphocytosis 
in  the  blood  of  Basedow  patients,  and  Caro,  in  1907,  reported  similar 
findings  in  one  case,  it  was  Kocher,  however,  who,  in  1908,  gave  these 
findings  their  true  significance,  and  considered  them  as  the  result  of  the 
disease.  Since  then  a  number  of  authors  have  published  the  results  of 
their  investigations  upholding  these  conclusions.  Important  information 
can  be  gotten  by  the  methodical  examination  of  the  blood  in  Graves' 
disease.  These  examinations  should  always  be  made  with  the  patient's 
stomach  empty  in  order  to  avoid  the  alimentary  leukocytosis.  The 
best  time  is  in  the  morning  before  breakfast.  The  chief  characteristics 
of  the  blood  in  Graves'  disease  are,  leukopenia,  hyperlymphocytosis,  and 
hypopolynucleosis. 

We  consider  as  normal,  blood  which  contains  about  5,000,000  red 
corpuscles  for  men,  and  about  4,500,000  for  women;  7000  to  8000  leuko- 
cytes; 70  to  75  per  cent,  polynuclears;  20  to  25  per  cent,  small  and 
large  lymphocytes;  3  to  5  per  cent,  mononuclears;  1  to  3  percent,  eosino- 
philes;  and  0.5  per  cent,  mast  cells.  W7e  shall  consequently  speak 
of  leukocytosis  when  the  number  of  leukocytes  goes  above  8000,  and  of 
leukopenia  when  the  number  goes  below  7000;  of  hyperpolynucleosis 
when  the  number  of  polynuclears  goes  above  75  per  cent.,  and  of  hypo- 
polynucleosis when  the  number  goes  below  75  per  cent.;  of  hyperlympho- 
cytosis when  the  number  of  lymphocytes  goes  above  25  per  cent.,  and  of 
hypolymphocytosis  when  this  number  goes  below  20  per  cent. 

This  being  agreed  upon,  let  us  see  what  are  the  characteristic  changes 
found  in  the  blood  of  Graves'  patients. 

The  number  of  red  blood  cells  is  usually  normal.  Not  infrequently, 
especially  in  young  women,  this  number  is  higher  than  normal,  running 
between  5,000,000  and  6,000,000  per  cubic  centimeter.  The  hemoglobin 
content  is  usually  normal.  There  may,  however,  be  a  slight  degree  of 
anemia  in  advanced  cases  of  thyrotoxicosis.  The  anemia  seems  not  to 
be  dependent  upon  the  thyrotoxicosis  itself,  but  must  be  regarded  as  a 
secondary  complication  due  to  the  disturbed  nutrition. 

The  most  important  changes  in  the  blood  formula  are  found  in  tin- 
number  and  relative  proportion  of  the  white  cells.     As  said  beforej  the 


350  BLOOD  CHANGES  IN  BASEDOW'S  DISEASE 

total  number  of  leukocytes,  as  a  rule,  is  diminished;  leukopenia  is 
present.  The  lowest  rate  I  have  found  was  3000;  Kocher  found  it  as 
low  as  2000;  at  the  same  time  the  number  of  lymphocytes  and  mono- 
nuclears is  increased  materially.  We  have,  consequently,  a  hyper- 
lymphocytosis:  the  highest  rate  I  have  found  was  75  per  cent.  On  the 
other  hand,  the  polynuclears  are  always  found  diminished  in  a  more  or 
less  degree;  their  lowest  rate  seen  was  28  per  cent.;  we  have,  conse- 
quently, a  hypopolynucleosis.  It  is  apparent  that  the  increase  in  the 
number  of  lymphocytes  takes  place  at  the  cost  of  the  number  of  poly- 
nuclears. If  divergences  are  still  found  among  authors  concerning  these 
blood  findings,  it  is  due  principally  to  the  fact  that  it  is  not  yet  clear 
to  everybody  how  to  classify  the  mononuclears  which  in  certain  cases 
show  great  variations.  The  eosinophiles  are  sometimes  found  increased 
in  Basedow's  disease,  but  this  is  not  a  constant  finding,  and  has  no  special 
clinical  diagnostic  value.  Mast  cells  and  transitional  forms  are  not 
materially  affected.  The  behavior  of  the  platelets  in  thyrotoxicosis  is  a 
chapter  which  still  remains  to  be  investigated. 

In  the  fruste  forms  of  thyrotoxicosis,  the  same  changes  appear,  but 
on  a  smaller  scale.  In  simple  goiter  unaccompanied  by  hyper-  or  hypo- 
thyroidism symptoms,  the  blood  formula  remains  normal. 

These  laboratory  findings  are  of  good  diagnostic  and  prognostic 
value.  In  doubtful  cases  where  the  diagnosis  of  thyrotoxicosis  is  not 
yet  certain,  a  slight  degree  of  leukopenia,  of  hyperlymphocytosis,  and 
of  hypopolynucleosis,  will  be  of  great  help  in  deciding  whether  we  have 
to  deal  with  a  thyrotoxic  condition  or  not;  the  same  is  true  for  the  prog- 
nosis. A  marked  leukopenia,  a  high  lymphocytosis,  a  marked  hypo- 
polynucleosis, will  show  that  the  case  is  a  serious  one.  A  high  percent- 
age of  lymphocytes  without,  or  with  only  a  moderate,  leukopenia  is  of 
good  prognostic  value,  whereas  a  marked  leukopenia  with  a  low  per- 
centage of  lymphocytes  must  be  regarded  as  of  bad  prognosis.  Hyper- 
lymphocytosis seems  to  be  more  or  less  dependent  upon  the  severity  of 
the  disease,  being  moderate  in  the  early  stage,  increasing  with  the  inten- 
sity of  the  thyrotoxicosis,  and  diminishing  gradually  when  the  condi- 
tion is  getting  better.  The  change  in  the  blood  may  be  followed  beau- 
tifully in  operative  cases.  The  same  day  of  the  operation  the  lympho- 
cytes diminish  materially  while  the  polynuclears  increase;  on  the  fol- 
lowing days,  however,  the  blood  formula  returns  to  its  previous  normal 
pathological  condition  and  only  then  improves  gradually  in  direct 
proportion  with  the  disease  and  usually  becomes  normal  in  the  fully 
cured  cases.  If,  in  the  apparently  cured  cases,  the  blood  formula  still 
remains  abnormal,  it  is  either  because  there  is  still  some  degree  of  thyro- 
toxicosis, or  because  the  hyperthyroidism  is  gradually  passing  into  one 
of  hypothyroidism.  Coagulability  of  the  blood  will  then  be  the  decisive 
argument  which  will  tell  which  one  of  the  two  conditions  we  have  to 


BLOOD  CHANGES  IN  BASEDOW'S  DISEASE  351 

deal  with.     The  return  to  normal  of  the  blood  formula  is  one  of  the  best 
signs  of  cure. 

This  picture  of  the  blood  in  Basedow's  disease,  according  to  Kocher, 
is  the  direct  result  of  thyrotoxicosis,  either  because  the  thyroid  throws 
directly  into  the  blood  stream  an  increased  number  of  lymphocytes,  or 
because  the  thyroid  secretion  stimulates  the  function  of  the  lymphatic 
system.  These  views  seem  to  be  upheld  by  Potrowsky,  who  found  that 
after  total  removal  of  the  thyroid  in  dogs,  the  small  lymphocytes  entirely 
disappeared  from  the  blood.  These  views  are  corroborated,  too,  by  the 
fact  that  thyroid  feeding  and  the  intravenous  injection  of  thyroid  extract 
are  always  accompanied  by  a  hyperlymphocytosis  and  a  hypopolv- 
nucleosis;  finally,  the  changes  in  the  blood  formula  and  its  return  to 
normal  after  operation,  are  the  strongest  indication  that  Basedow's 
formula  is  dependent  upon  the  thyroid  pathology.  Were  this  all,  every- 
thing so  far  would  be  lovely  in  all  these  explanations.  But  we  must 
not  overlook  the  fact  that  we  find  the  same  blood  changes  in  thyroid 
insufficiency.  There  the  thyrotoxicosis  can  no  longer  be  incriminated. 
What  is  the  explanation  ?     Nescio. 

Lately  some  authors  are  inclined  to  believe  that  hyperlymphocy- 
tosis, hypopolynucleosis,  and  leukopenia  are  not  altogether  dependent 
upon  the  thyroid  changes,  but  may  be  the  result  of  alterations  of  the 
thymus.  Klose  maintains  that  these  blood  changes  are  due  altogether 
to  thymic  hyperplasia.  Against  such  views  I  could  cite  two  of  my 
fatal  cases,  in  which  the  blood  formula  was  normal  although  both 
patients  had  very  great  thymic  hyperplasia,  as  was  shown  by  post- 
mortem. It  is  true  that  these  two  cases  were  not  suffering  from  thyro- 
toxicosis, but  only  from  the  mechanical  symptoms  caused  by  the  large 
goiter.  As  we  know  that  in  patients  with  simple  colloid  or  cystic  goi- 
ters, unaccompanied  by  thyrotoxic  symptoms,  the  blood  formula  remains 
normal,  possibly,  the  same  might  be  true  for  thymic  hyperplasia.  We 
may  have  cases  in  which  thymic  hyperplasia  causes  only  mechanical 
disturbances,  and  other  cases  in  which  it  causes  thymotoxic  disturbances; 
these  cases  only  would  then  show  changes  in  the  blood  formula.  These 
views  will  have  to  be  corroborated  by  further  researches.  One  fact, 
however,  is  certain:  the  changes  in  the  blood  formula  do  not  always  go 
hand  in  hand  with  the  amelioration  of  the  disease.  There  are  thyrotoxic 
cases  which  can  be  considered  as  clinically  cured,  and  which  still  show 
even  years  after,  the  characteristic  changes  of  the  blood  picture.  Hence 
the  conclusion  of  a  number  of  authors  that  these  changes  in  the  blood 
are  dependent  upon  thymic  hyperplasia.  Furthermore,  as  in  myxedema, 
the  blood  picture  is  similar  to  the  one  seen  in  hyperthyroidism,  and 
since  in  myxedema  the  thymus  is  nearly  always  hyperplastic,  Klose 
considers  this  as  another  proof  that  the  blood  changes  are  due  to  th\  mic 
hyperplasia,  and  that  they  are  not  caused  by  the  thyroid  pathology. 


352  BLOOD  CHANGES  IN  BASEDOW'S  DISEASE 

In  conclusion  we  may  say  that  the  question  is  still  an  open  one.  It 
would  be  a  mistake  to  think  that  lymphocytosis  is  pathognomonic  for 
a  thyroid  or  thymic  condition  only.  Lymphocytosis  has  been  found  a 
number  of  times  in  connection  with  diseases  of  other  glandular  organs 
such  as  the  liver,  kidneys,  pancreas,  parotids,  etc.,  consequently,  before 
giving  any  diagnostic  value  to  lymphocytosis,  we  should  carefully  elimi- 
nate all  other  possibilities  which  might  cause  that  condition.  On  the 
other  hand,  the  absence  of  lymphocytosis  does  not  necessarily  mean 
that  we  must  exclude  thyrotoxicosis,  because  sometimes  changes  in  the 
blood  formula  do  not  occur  even  in  typical  thyrotoxic  cases.  Although 
exceedingly  important,  and  almost  pathognomonic,  these  blood  changes 
must  be,  however,  carefully  interpreted  and  their  true  origin  and  real 
value  established  in  every  given  case. 

Anyone  who  has  had  a  great  deal  to  do  with  Graves'  disease  must 
have  encountered  once  in  awhile  a  more  or  less  severe  case  in  which  an 
intercurrent  disease  of  moderate  severity  has,  however,  proved  fatal  to 
the  patient.  Not  very  long  ago  I  saw  a  case  in  which  a  moderate 
degree  of  tonsillitis  terminated  fatally  without  there  being  any  apparent 
cause  or  complication  to  explain  such  a  death.  The  reason  must  be 
found,  very  likely,  in  the  diminished  number  of  polynuclears.  We  know 
that  these  polynuclears  are  the  defenders  upon  which  our  organism  counts 
when  it  is  invaded  by  infectious  agents.  They  respond  at  once  by 
millions  to  the  call;  they  contain  antitoxic,  peptic,  and  oxydative  fer- 
ments, and  have  marked  chemotactic  properties.  In  Graves'  disease 
the  polynuclears  being  greatly  diminished  in  number,  and  possibly 
inhibited  by  the  thyrotoxin,  the  means  of  defense  of  the  organism  are 
reduced.  This  will  explain  why  thyrotoxic  patients  are  so  vulnerable 
to  acute  infections,  which  in  ordinary  conditions,  would  be  warded  off 
easily.  It  is  true  that  in  the  majority  of  such  thyrotoxic  conditions, 
whenever  an  acute  infection  takes  place,  the  number  of  lymphocytes 
diminishes  in  order  to  allow  the  polynuclears  to  increase.  As  soon, 
however,  as  the  acute  process  is  past,  the  blood  formula  returns  to  its 
previous  conditions,  namely,  hyperlymphocytosis  takes  the  upper  hand, 
and  the  polynuclears  again  becoming  reduced  in  number.  In  a  few  cases, 
however,  leukocytosis  and  hyperpolynucleosis  do  not  take  place,  or 
occur  in  such  a  small  degree  that  the  organism  is  unable  successfully 
to  meet  the  invaders;  it  offers  to  them  no,  or  very  little  resistance;  the 
battle  is  really  lost  before  being  fought. 

Coagulability  of  the  Blood. — Kottmann,  Lidsky  and  Kostlivy  found 
that  in  Graves'  disease  the  blood  shows  a  diminished  coagulability, 
whereas,  in  hypothyroidism  the  power  of  coagulation  of  the  blood  is 
materially  increased.  This  fact  will  perhaps  explain  why  operations  for 
Graves'  disease  are  so  bloody.  This  difference  in  the  coagulating  power 
of  the  blood  is  due,  according  to  Kottmann,  to  the  fact  that  blood  in 


A  DREXA  LI  X  EMI.  1  353 

hypothyroidism  contains  a  diminished  amount  of  antithrombin,  hence 
its  increased  coagulability,  whereas  in  Basedow  the  antithrombin  con- 
tent is  increased,  hence  its  diminished  coagulability.  According  to 
Doyon,  antithrombin  is  given  off  by  the  liver.  Kottmann  claims  that 
in  Basedow's  disease  the  viscosity  of  the  blood  is  increased.  This  dif- 
ference in  the  coagulability  of  the  blood  in  hyperthyroidism  and  hypo- 
thyroidism, according  to  Kocher,  is  a  constant  one,  and  an  excellent 
differential  diagnostic  symptom  which  should  be  resorted  to  in  the 
doubtful  cases.  Indeed,  since  the  blood  changes  which  used  to  be  con- 
sidered as  pathognomonic  for  Graves'  disease  such  as  leukopenia, 
hyperlymphocytosis,  hypopolynucleosis,  are  equally  found  in  hypo- 
thyroidism, the  changes  in  the  blood  formula  lose  their  diagnostic  value. 
In  doubtful  cases  only  the  coagulability  of  the  blood  will  be  the  deciding 
element.  It  must  be  said,  however,  that  Julius  Bauer  who  repeated  the 
same  experiments  as  Kottmann,  did  not  obtain  the  same  results. 

Adrenaline  mi  a. — It  is  more  or  less  universally  conceded  today  that 
the  suprarenal  bodies  produce  epinephrin,  and  that  this  adrenalin 
reaches  the  blood  and  is  used  to  maintain  the  tonicity  of  the  vascular 
system.  Experimentally  it  has  been  found  that  the  blood  coming  from 
the  suprarenal  veins  contains  epinephrin,  and  the  conclusion  has  been 
drawn  that  the  blood  contains  more  or  less  adrenalin,  and  that  this 
substance  varies  with  the  pathological  condition. 

Epinephrin  has  strong  mydriatic  properties  and  very  likely  exerts 
its  action  by  influencing  directly  the  muscular  cells  of  the  dilatator 
muscles  of  the  ins,  and  possibly  by  direct  action  upon  the  sympathetic 
nerve.  The  action  of  the  epinephrin  may  be  considered  as  analogous 
to  the  electrical  excitation  of  the  sympathetic  nerve.  Adrenalin  mydri- 
asis is  found  in  all  the  conditions  in  which  the  sympathetic  system 
is  excited.  It  is  found  further  in  pathological  conditions  of  the 
pancreas,  hyperthyroidism,  diabetes  mellitus;  it  is  furthermore  found 
in  many  pathological  conditions  of  the  stomach,  intestines,  in 
lesions  of  the  central  nervous  system,  and  of  the  meningeal  membranes. 
In  such  conditions  mydriasis  is  very  likely  due  to  an  irritation  of  the 
sympathetic  system  by  the  pathological  condition. 

The  methods  of  determining  the  adrenalin  content  of  the  blood  are 
numerous,  but  none  are  so  very  reliable.  The  test  method  which  I  have 
adopted  is  the  Ehrmann  method.  This  method  consists  in  enucleating 
the  eye  of  a  frog,  if  possible,  the  rana  esculentay  and  plunging  this  eye 
into  the  blood  serum  of  the  patient.  The  time  which  elapses  from  the 
moment  in  which  the  eye  has  been  put  into  the  serum  to  the  moment 
when  the  pupil  reaches  the  maximal  dilatation  is  carefully  noted,  and 
as  a  scale  has  been  previously  made  of  different  solutions  of  epinephrin 
showing  the  length  of  time  it  takes  a  given  solution  of  epinephrin  to 
23 


354  BLOOD  CHANGES  IN  BASEDOW'S  DISEASE 

dilate  the  pupil  to  its  maximum,  it  is  therefore  easy  to  find  out  the 
quantity  of  epinephrin  contained  in  the  blood  serum.  This  method,  of 
course,  is  not  an  accurate  one.  Another  objection  which  may  be  raised 
is  that  it  is  not  at  all  certain  that  the  dilatation  of  the  pupil  is  due  to 
the  epinephrin;  it  may  be  due  to  the  other  sympatheticotonic  substances 
which  belong  to  the  same  class  as  adrenalin,  such  as  the  pituitary  and 
thymus  extracts,  and  which,  according  to  Biedl,  Zandler,  and  Ranze, 
give  also  the  Meltzer-Ehrmann  reaction.  It  was,  however,  the  best 
method  I  had  at  my  disposal  at  the  time.  From  investigations  made  in 
a  great  many  cases  with  the  method,  I  am  unable  to  draw  any  practical 
information,  because  in  many  of  the  severe  cases  of  Graves'  disease, 
the  epinephrin  content  of  the  blood  was  increased,  but  in  other  cases 
just  as  severe,  it  was  only  light  or  negative.  It  has  been  asserted  that 
hyperlymphocytosis  combined  with  absence  of  epinephrin  in  the  blood 
is  of  bad  prognosis.  In  my  own  experience  I  have  been  unable  to 
convince  myself  that  this  is  true. 

Hyperglycemia. — Tachaus  has  shown  that  the  blood  of  normal  indi- 
viduals contains  an  average  of  0.086  per  cent,  of  sugar.  If  these  normal 
individuals  are  fed  with  100  grains  of  sugar,  no  increase  in  the  sugar 
content  of  the  blood  takes  place.  In  Basedow  patients,  on  the  contrary, 
as  soon  as  they  are  fed  with  sugar,  the  sugar  content  of  the  blood  increases 
to  double  or  more  of  its  normal  rate.  This  hyperglycemia  is  consequently 
not  a  primary  one,  but  must  be  regarded  as  an  alimentary  hypergly- 
cemia; it  is  very  likely  of  thyroid  origin,  as  it  can  be  produced  more  or 
less  at  will  by  ingestion  of  thyroid  extract.  It  gradually  diminishes  as 
the  thyrotoxic  condition  improves.  Flesch  claims  that  there  is  an 
antagonism  between  hyperglycemia  and  lymphocytosis:  the  stronger  the 
hyperglycemia,  the  less  the  lymphocytosis,  and  vice  versa. 

Antitrypsin  Content  of  the  Blood. — Walli  found  that  antitrypsin  in 
the  blood  of  normal  individuals  is  very  rarely  present.  In  Basedow 
patients,  however,  it  seems  to  be  constant.  The  clinical  picture  of  hyper- 
thyroidism need  not  be  fully  developed  in  order  to  have  a  positive 
finding  of  antitrypsin,  since  the  reaction  is  present  in  the  early  incipient 
cases.  The  antitrypsin  content  is  in  direct  relation  to  the  gravity  of  the 
disease.  If  this  test  should  prove  correct,  it  would  be  of  excellent 
diagnostic  value  when  the  diagnosis  is  doubtful. 

Complement-fixation. — Papazoula  has  shown  that  the  blood  serum 
of  Basedow  patients  was  able  to  fixate  the  complement  when  mixed 
with  antigen  extracted  from  thyrotoxic  goiters.  According  to  this 
author  the  thyroid  gland  in  that  case  acts  as  an  antigen,  thus  causing 
the  formation  of  antibodies.  Hence  the  conclusion  that  in  Graves' 
disease  the  thyroid  secretion  is  not  only  quantitatively  but  also  quali- 
tatively affected,  which  is  an  argument  in  favor  of  dysthyroidism. 


CHAPTER   XXXII. 
DISTURBANCES   IN   METABOLISM. 

Loss  of  Flesh. — Loss  of  flesh  is  one  of  the  most  constant  and  most 
important  symptoms  in  Graves'  disease.  It  goes  hand  in  hand  with 
muscular  weakness.  This  loss  of  flesh  may  be  either  a  very  rapid  or  a 
very  gradual  one,  and  it  is,  as  a  rule,  one  of  the  earliest  symptoms  of 
the  disease.  If  gastro-intestinal  disturbances  such  as  vomiting,  diar- 
rhea, etc.,  are  present,  the  loss  of  flesh  will  of  course  be  far  more  pro- 
nounced, but  in  a  number  of  conditions  there  is  no  apparent  cause  for 
the  loss  of  flesh.  It  may  even  occur  despite  a  good  appetite  and  a  very 
liberal  diet. 

Fr.  Miiller  has  shown  that  this  loss  of  flesh  is  due  to  the  fact  that  the 
nitrogen  losses  are  increased  far  above  the  normal.  Not  only  the  metab- 
olism of  albumin  is  increased,  but  the  consumption  of  fat  and  carbo- 
hydrates is  also  considerably  exaggerated.  Steyrer  proved  that  in  Graves' 
disease  there  is  an  increased  production  of  calories  due  to  the  metabolism 
of  albumin  and  fat.  This  hyperproduction  of  calories  is  independent  of 
diet  since  it  occurs  even  when  the  patient  remains  fasting;  spells  of 
nervousness,  however,  increase  it  very  materially.  Magnus-Levy  has 
shown  that  in  Graves'  disease  the  gaseous  exchanges  are  increased, 
namely,  that  C02  excretion  is  materially  increased.  While  the  quantity 
of  sodium  chloride  remains  about  normal,  the  amount  of  phosphates 
existing  in  the  urine  of  Basedow  patients  is  greatly  increased. 

We  may  say  that  in  Graves'  disease  the  metabolism  is  profoundly 
disturbed,  and  that  the  various  oxydating  processes  are  constantly  and 
always  materially  increased.  The  patient  is  "burning  the  candle  at 
both  ends."  He  keeps  up  the  fire  by  consuming  the  albumin,  fats,  and 
carbohydrates  of  the  body.  If  the  patient  is  able  to  offset  the  losses  by 
a  good  diet,  all  well  and  good:  the  equilibrium  between  the  intake  and 
exchanges  will  remain  more  or  less  undisturbed;  if  not,  loss  of  flesh  will 
follow.  If  loss  of  flesh  nevertheless  occurs  despite  a  free  diet,  it  will  be 
due  to  an  impaired  resorption  and  assimilation  of  the  gastro-intestinal 
tract.  This  increase  in  all  the  oxydating  processes  is  most  likely  of 
toxic  origin,  either  because  it  stimulates  the  centers  of  heat,  or  because 
it  influences  the  nervous  system  controlling  metabolism. 

Temperature.  With  the  increase  of  all  the  oxydating  processes,  we 
might   then   expect  an   increase  of  the  bodily  tempt  ratine.     And  so  it 


356  DISTURBANCES  IN  METABOLISM 

happens.  Rise  in  temperature  is  frequently  seen  in  Basedow  patients. 
It  is  most  inconstant  and  most  irregular;  it  goes  and  comes,  may  last 
over  a  few  days  and  then  become  normal  again.  There  seems  to  be  no 
apparent  cause  for  this.  Temperature,  however,  seems  to  follow  the 
periods  of  exacerbation  of  the  disease.  It  is,  as  a  rule,  not  high,  evoluting 
around  ioo,  seldom  goes  above  101,  and  does  so  only  when  the  case  is  a 
very  severe  one.  Although  the  increase  in  the  oxydating  processes  may 
be  fully  incriminated,  this  rise  in  temperature  is  most  likely  due  to  some 
thyrotoxic  influence  upon  the  nervous  centers  regulating  the  bodily 
temperature. 

GLYCOSURIA    AND    DIABETES    IN    GRAVES'    DISEASE. 

As  a  general  fact  sugar  may  be  found  in  the  urine  of  any  individual 
after  a  certain  amount  of  sugar  has  been  consumed.  We  know  that 
the  coefficient  of  absorption  for  sugar  varies  with  each  normal  individ- 
ual; as  soon  as  this  coefficient  is  overstepped,  then  sugar  appears  in  the 
urine.  This  is  what  we  call  alimentary  glycosuria.  In  diabetes,  on  the 
other  hand,  sugar  is  found  in  the  urine  despite  the  fact  that  sugar  and 
carbohydrates  are  withheld  from  the  patient.  It  is  not  enough,  how- 
ever, once  in  awhile  to  find  sugar  in  the  urine  of  a  patient  in  order  to 
diagnose  diabetes,  since  we  might  erroneously  consider  as  diabetes  a 
transient  form  of  alimentary  glycosuria.  Glycosuria  must  last  for  a  long 
time  and  be  independent  of  food,  before  it  can  be  considered  as  true  dia- 
betes; furthermore,  diabetes  is,  as  a  rule,  accompanied  by  polyuria  and 
thirst. 

In  Graves'  disease  alimentary  glycosuria  is  far  more  frequent  than 
diabetes:  Hirschl  found  it  in  30  per  cent,  and  Schulze  in  25  per  cent,  of 
their  respective  cases.  These  figures  may  not  represent  the  true  percent- 
ages for  all  cases  known  but  the  fact  remains  that  alimentary  glycosuria 
is  comparatively  frequent  in  Graves'  disease. 

Far  more  frequent  than  the  alimentary  glycosuria  is  that  one  which 
appears  after  small  doses  of  adrenalin  are  given  to  a  Basedow  patient 
who  has  just  ingested  100  grams  of  sugar.  According  to  Schulze, 
this  alimentary  glycosuria  of  adrenal  origin  appears  in  80  per  cent,  of 
the  patients. 

True  diabetes,  on  the  other  hand,  is  more  rare  and,  according  to 
reliable  statistics,  is  not  found  in  more  than  3  per  cent,  of  the  cases. 
It  usually  occurs  after  Graves'  disease  is  far  advanced.  The  quantity 
of  sugar  found  in  the  urine  is,  as  a  rule,  moderate;  in  severe  cases, 
however,  it  may  be  very  large. 

The  presence  of  diabetes  in  Graves'  disease  must  be  always  regarded 
as  a  serious  complication  and  of  bad  prognosis.     Ordinarily  as  soon  as 


GLYCOSURIA  AXD  DIABETES  IN  GRAVES'  DISEASE  357 

diabetes  occurs,  the  patient  begins  to  lose  flesh  and  complains  of  an 
intense  muscular  weakness.  Despite  the  fact  that  diabetes  is  far  more 
frequent  in  men,  the  combination  of  Basedow  and  diabetes  is  more 
frequently  seen  in  women. 

To  claim  that  all  cases  of  diabetes  and  alimentary  glycosuria  compli- 
cating Graves'  disease  are  of  thyroid  origin  would  be  folly.  A  number 
of  them  supervene  as  an  independent  complication  and  have  no  relation 
to  thyrotoxicosis.  This,  however,  is  not  true  for  all  cases.  A  number  of 
clinical  as  well  as  experimental  observations  seem  to  prove  that  there 
is  an  intimate  relation  between  the  thyroid  and  glycosuria.  Beclere 
reports  the  case  of  a  male,  thirty-two  years  old,  who  was  suffering  from 
myxedema.  In  the  course  of  n  days  this  patient  absorbed  93  fresh 
thyroid  glands  of  sheep;  palpitation,  tremor,  dyspnea,  profuse  perspira- 
tion, insomnia,  and  polyuria  became  very  marked.  Urine  analysis 
showed  albumin  and  sugar.  Nothaft  reports  the  observation  of  a  man, 
forty-three  years  old,  who  in  order  to  get  thinner  took  a  thousand  tablets 
of  thyroid  extract  of  5  grains  each  in  five  weeks.  After  three  weeks  the 
patient  began  to  develop  marked  exophthalmic  symptoms;  the  urine 
contained  1  per  cent,  of  sugar.  F.  Miiller  saw  a  patient  who  had  a 
light  form  of  Graves'  disease,  and  who  was  fed  with  thyroid  extract 
tablets;  symptoms  of  hyperthyroidism  became  extremely  marked. 
Severe  diabetes  developed  and  death  ensued.  In  a  myxedematous 
patient  fed  with  thyroid  extract,  Ewald  found  4  per  cent,  of  sugar.  This 
sugar  could  be  made  to  appear  and  disappear  at  will  by  regulating  the 
thyroid  feeding.  Von  Noorden  reports  17  cases  of  obesity  treated  with 
thyroid  extract;  in  5  of  them  sugar  was  found  during  the  treatment. 
A  number  of  other  clinical  as  well  as  experimental  cases  can  be  cited  in 
which  thyroid  feeding  had  caused  glycosuria.  In  the  presence  of  all 
these  facts  it  is  difficult  not  to  admit  that  there  is  a  relation  between 
the  thyroid  and  glycosuria,  and  that  in  Graves'  disease  the  presence  of 
sugar  in  the  urine  must  be  referred  to  the  hyperfunction  of  the  thyroid, 
combined  with  an  exaggerated  excitation  of  the  sympathetic  nerve  and  a 
pancreatic  insufficiency.  We  have  then  to  deal  with  a  thyreogene  glycosuria. 
Thyreogene  glycosuria  is  characterized  by  the  fact  that  it  develops 
with  Graves'  disease  and  disappears  with  its  improvement.  Thyreo- 
gene glycosuria  seems  to  be  more  frequent  in  traumatic  Basedow  and 
is  often  combined  with  other  disturbances  in  the  resorption  of  fat.  That 
the  thyroid  intervenes  in  the  production  of  glycosuria  is  so  much  more 
plausible  since  glycosuria  may  be  caused  by  other  glands  than  the 
thyroid,  as  for  instance,  the  hypophysis,  suprarenal  bodies,  liver,  etc. 

Polyuria.  Polyuria  is  often  seen  in  Graves'  disease;  it  is  sometimes 
an  early  symptom  and  occurs  without  any  apparent  pathological  condi- 
tion of  the  kidneys.     It  is  very  likely  a  symptom  of  nervous  origin. 


358  DISTURBANCES  IN  METABOLISM 

Polydipsia. — Knowing  how  much  Basedow  patients  perspire  and 
often  suffer  from  diarrhea,  vomiting,  and  polyuria,  in  short,  knowing 
that  they  are  losing  fluids  in  many  ways,  no  one  will  wonder  that  they 
often  complain  of  thirst,  and  that  they  drink  water  abundantly.  How- 
ever, the  etiology  of  polydipsia  is  not  quite  so  simple,  and  must  be 
regarded,  too,  as  a  symptom  of  nervous  origin,  probably  due  to  the 
irritation  of  some  buboprotuberential  centers. 

Albuminuria. — Traces  of  albumin  are  sometimes  found  in  Graves' 
disease;  they  are  not  connected,  as  a  rule,  with  any  disease  of  the  kid- 
neys, as  no  cylinders  and  no  epithelial  cells  are  present  in  the  urine. 
It  is  most  likely  of  toxic  origin,  and  disappears  as  soon  as  the  condition 
subsides. 

THYROTOXICOSIS  IS  A  CHRONIC  DISEASE. 

Now  that  we  have  studied  all  the  symptoms  and  followed  their 
development,  although  at  first  the  whole  symptom-complex  seemed 
stormy  and  erratic,  we  cannot  but  be  impressed  by  one  fact,  namely, 
that  the  disease  is  essentially  chronic.  No  matter  how  various  and 
changing  the  symptoms  are,  no  matter  if  a  given  case  apparently  changes 
its  physiognomy  hundreds  of  times  during  its  course,  and  no  matter  if 
at  times  some  symptoms  become  acute  and  subside  again,  nevertheless 
the  general  tendency  of  the  entire  process  is  to  be  a  chronic  one.  The 
disease  follows  a  cycle,  which  grossly  speaking  can  be  said  to  be  identical 
with  itself.  It  usually  begins  insidiously,  reaches  gradually  its  full  de- 
velopment, shows  periods  of  betterment,  alternating  with  spells  of 
exacerbation,  lasts  years  and  then  finally  either  takes  a  decisive  turn  for 
the  best,  or  terminates  by  death.  No  matter  how  various  its  manifes- 
tations are,  the  main  symptoms  are  always  constant  in  their  character. 
Thus  tachycardia,  for  instance,  will  remain  identical  with  itself  throughout 
the  entire  course  of  the  disease  so  as  to  resemble  no  other  form  of 
tachycardia.  The  same  is  true  for  tremor.  Vomiting  and  diarrhea  may 
last  weeks  and  months,  may  come  and  go  without  changing  in  their 
nature,  and  without  leading  into  a  gastritis  or  an  enteritis.  And  so  on 
for  the  other  symptoms. 

FULMINATING  FORMS    OF  GRAVES'  DISEASE. 

That,  however,  one  will  meet  once  in  a  while  with  rapidly  evolving 
cases  of  Graves'  disease  there  is  no  doubt:  the  condition  begins,  evoluates, 
and  terminates  by  death  in  a  very  short  time,  within  a  few  weeks  or 
months.  From  its  inception  the  disease  takes  on  a  malignant  form; 
tachycardia  and  nervousness  are  intensely  marked,  and  the  gastro- 
intestinal symptoms  are  especially  alarming;  vomiting  and  diarrhea  are 


ALL  THYROTOXIC  SYMPTOMS  ARE  WORSE  IN  THE  MORXIXG      359 

continuous  and  become  uncontrollable.  The  patient  is  profoundly 
thyrotoxic,  and  since  little  or  no  food  is  retained,  the  patient  sinks 
rapidly,  and  death  follows  after  a  few  weeks,  with  marked  symptoms  of 
acidosis.  In  all  the  fulminating  forms  of  Graves'  disease  which  I  have 
seen,  the  gastro-intestinal  symptoms  were  always  the  leading  ones. 

ALL  THE  THYROTOXIC  SYMPTOMS  ARE  WORSE  IN  THE  MORNING. 

I  believe  anyone  who  has  had  wide  experience  with  Graves'  disease 
will  agree  with  W.  H.  Thomson  when  he  says,  "  If  it  be  asked  what  are  the 
most  peculiar  or  most  characteristic  features  of  Graves'  disease,  I  would 
answer  that  next  to  its  specific  tachycardia  is  the  morning  exacerbation 
of  its  symptoms."  No  careful  observer  can  fail  to  be  impressed  by  this 
singular  phenomenon.  I  have  looked  for  that  symptom  in  all  cases  of 
goiter  which  have  come  under  my  observation,  and  I  must  say  that  in 
the  great  majority  of  cases,  no  matter  if  they  were  true  cases  of  Graves' 
disease  or  simple  goiters  complicated  with  some  thyrotoxic  symptoms, 
this  symptom  was  nearly  always  present.  Without  any  hesitation  the 
patients  admitted  that  they  were  decidedly  worse  in  the  morning  and 
would  get  better  toward  evening.  When  they  rose  they  felt  more  tired 
than  when  they  went  to  bed;  they  complained  of  an  intense  general 
depression;  they  were  "good  for  nothing."  All  their  thyrotoxic  symptoms 
seemed  to  be  more  exaggerated,  and  tremor  became  more  marked,  so  as 
to  prevent  the  patient  from  doing  any  work  in  the  morning,  whereas  in 
the  afternoon  such  work  was  possible.  Palpitations  and  nervousness 
became  more  intense  but  subsided  toward  evening.  Headaches,  too,  were 
more  accentuated  in  the  morning,  and  the  patients  complained  of  heavy 
weights  upon  their  spirits,  and  of  a  beclouding  of  the  mind  so  as  to 
preclude  the  possibility  of  mental  work,  or  of  concentration  of  the  mind 
until  late  in  the  afternoon.  If  gastro-intestinal  symptoms  were  present, 
vomiting  and  diarrhea  underwent  marked  exacerbations  toward  morn- 
ing and  subsided  toward  evening.  In  short,  the  entire  chain  of  thyro- 
toxic symptoms  became  aggravated  in  the  morning.  This  symptom  is 
very  peculiar  to,  and  almost  characteristic  of,  Graves'  disease.  Hys- 
teria has  nothing  to  do  with  its  production;  it  is  very  likely  due  to  some 
disturbance  in  the  biological  chemistry  of  the  organism,  more  marked 
at  that  time  of  the  day.  But  what  this  disturbance  really  is  and  why  it 
takes  place,  is  still  an  open  question. 


CHAPTER   XXXIII. 

FRUSTE   FORMS  OF   HYPERTHYROIDISM  OR   SMALL 
HYPERTHYROIDISM. 

It  is  not  usual  to  find  all  the  thyrotoxic  symptoms  ordinarily  seen 
in  Graves'  disease  equally  developed  in  the  same  case;  as  a  rule  some 
of  them  are  more  prominently  developed  than  others,  while  frequently, 
quite  a  few  even  fail  to  be  present.  In  these  cases,  however,  the  diag- 
nosis does  not  offer  great  difficulties  because  one  or  more  of  the  cardinal 
symptoms  will  clear  at  once  the  diagnosis.  Even  if  one's  judgment  has 
been  side-tracked,  as  a  rule,  the  general  physiognomy  of  the  case,  its 
course  of  development  and  its  behavior  will  soon  betray  its  true  nature. 
There  are  cases,  however,  which  require  a  great  deal  of  experience, 
sagacity  and  judgment  before  one  dares  to  venture  the  diagnosis  of 
thyrotoxicosis.  There  none  of  the  cardinal  symptoms  are  present,  or 
at  least  they  are  so  insufficiently  developed  that  a  diagnosis  of  thyro- 
toxicosis is  scarcely  warranted;  yet,  in  the  last  analysis  these  cases  are 
of  thyrotoxic  origin.  They  are  incomplete  forms  of  thyrotoxicosis;  they 
are  called  fruste,  or  incomplete  forms  of  hyperthyroidism.  They  consti- 
tute what  I  call  small  hyperthyroidism.  As  we  have  the  great  and  small 
hypothyroidism,  so  we  have  the  great  and  small  hyperthyroidism. 

These  fruste  cases  in  which  the  majority  of  the  classical  symptoms 
are  absent  are  very  apt  to  be  overlooked,  either  because  of  lack  of  experi- 
ence, or  because  these  cases  are  so  atypical  that  it  is  difficult  at  first 
to  trace  them  back  to  their  true  origin.  On  the  other  hand,  there  is  no 
doubt,  however,  that  these  fruste  forms  of  hyperthyroidism  are  far 
more  frequent  than  is.  generally  suspected.  If  they  were  all  recognized, 
it  would  be  found  that  they  constitute  a  substantial  percentage  of  the 
total  of  patients  seeking  medical  relief. 

An  incomplete  form  of  thyrotoxicosis  frequently  seen  is  that  one 
where  the  heart-rate  is  above  normal,  where  the  patient  complains  of  a 
general  throbbing  of  the  arteries,  or  of  palpitation.  At  the  same  time 
there  is  a  marked  instability  of  the  nervous  system,  yet,  physical  exami- 
nation of  the  nervous,  cardiac,  urinary,  and  other  systems  fails  to  reveal 
anything  pathological.  No  apparent  cause  can  be  found  to  explain  that 
condition.  Such  cases  are  often  only  fruste  forms  of  hyperthyroidism. 
If,  perchance,  one  is  able  to  detect  some  other  concomitant  thyrotoxic 
symptoms  such  as  possibly  a  small  thyroid  hypertrophy,  some  tremor, 
etc.,  then  doubt  is  no  longer  permissible;  this  is  a  fruste  form  of  hyper- 
thyroidism. 


HYPERTHYROIDISM  OR  SMALL  HYPERTHYROIDISM  361 

There  are  numbers  of  young  women  who,  at  the  time  of  puberty 
complain  of  palpitation,  tachycardia,  fatigue,  loss  of  energy,  and  of 
some  swelling  of  the  feet.  As  a  rule  the)'  are  regarded  as  chlorotic,  yet 
laboratory  findings  generally  show  that  the  blood  is  normal.  If  at 
the  same  time  such  patients  happen  to  have  occasional  rises  in  tempera- 
ture, and  if  they  also  complain  of  sweating,  they  are  very  apt  to  be 
considered  as  tuberculous  and  treated  accordingly.  However,  should  a 
careful  examination  be  made,  some  nervousness,  possibly  even  some 
psychic  disturbances  might  be  found — all  facts  showing  that  such 
patients  are  suffering  from  fruste  forms  of  hyperthyroidism  secondary 
to  the  maturation- of  their  genital  systems.  As  soon  as  the  genital  pro- 
cess is  settled  and  the  organism  has  found  its  equilibrium,  the  thyro- 
toxic syndrome  ordinarily  subsides  and  then  these  patients  again  regain 
their  health.  The  same  is  true  for  women  at  the  menopause.  The}'  com- 
monly complain  at  that  time  of  hot  flashes,  palpitation,  nervousness, 
tremor,  sweating,  of  occasional  gastro-intestinal  disturbances,  etc. 
Examination  reveals  a  moderate  degree  of  tachycardia,  little  or  no 
apparent  enlargement  of  the  thyroid,  and  no  ocular  symptoms.  Ovarian 
extracts  remain  without  effect.  Such  cases  are  regarded  as  nervous 
patients,  and  treated  with  all  the  tonics,  sedatives,  cardiac  stimulants, 
etc.,  imaginable.  Little  or  no  results  are  obtained  because  the  real 
cause  is  to  be  found  in  the  hyperfunction  of  the  thyroid.  These  cases 
are,  too,  fruste  forms  of  hyperthyroidism. 

Not  infrequently  we  see  patients  who  apparently  have  a  simple 
non-toxic  goiter  and  who  intermittently  may  complain  of  cardiovascular 
and  nervous  symptoms.  Once  in  awhile  they  may  have  an  occasional 
diarrhea  alternating  with  constipation.  This  condition  may  go  on  for 
years,  off  and  on,  periods  of  complete  welfare  alternating  with  periods 
of  thyrotoxicosis.  These  cases,  too,  are  fruste-  forms  of  hyperthyroidism. 
In  other  cases  there  is  apparently  no  thyroid  enlargement.  The  thyro- 
toxic symptoms  are  more  or  less  of  vague  nature,  characterized  by  some 
nervousness,  and  some  tremor,  by  periods  of  muscular  asthenia,  by 
occasional  palpitation,  and  occasionally  by  some  tachycardia  especially 
connected  with  physical  effort,  by  headaches,  and  at  times  by  indiges- 
tion or  hyperacidity,  and  by  some  occasional  menstrual  disturbances. 
All  these  symptoms  experience  periods  of  exacerbation  and  improve- 
ment. They  come  and  go;  the  syndrome  is  of  protean  type.  I  hese 
patients,  as  a  rule,  do  not  stand  easily  acute  infections,  they  do  not 
recover  as  quickly  as  others.  Any  psychic  shock,  even  of  moderate 
degree,  will  leave  on  them  traces  for  weeks  and  months,  while  a  normal 
individual  would  not  be  feazed  by  it.  Such  patients  arc-  treated  either 
for  gastro-intestinal  troubles,  or  for  menstrual  disturbances,  or  for 
nervousness,   etc.     No   or   very    little    improvement  is  ganu-d   by  such 


362         HYPERTHYROIDISM  OR  SMALL  HYPERTHYROIDISM 

therapeutics;  they  may  even  be  made  worse.  If,  however,  the  correct 
diagnosis  is  made,  and  the  case  regarded  as  a  fruste  form  of  hyper- 
thyroidism, and  the  correct  treatment  is  instituted,  these  patients  may 
be  greatly  benefited.  Every  medical  means  being  exhausted  in  vain,  I 
have  operated  a  few  of  them  and  cured  them  entirely. 

There  are  fruste  forms  of  hyperthyroidism  due  to  gastro-intestinal 
ptosis  causing  an  auto-intoxication  which  in  turn  results  in  the  produc- 
tion of  a  group  of  thyrotoxic  symptoms.  These  symptoms  may  be  of 
severe  nature,  and  are  especially  characterized  by  nervousness,  palpi- 
tation, tremor,  loss  of  flesh,  and  intense  asthenic  symptoms.  They 
may  resist  every  medical  treatment.  One  of  my  most  grateful  patients 
is  a  young  woman  who  had  a  marked  gastro-intestinal  ptosis,  causing 
spells  of  weakness,  muscular  asthenia,  nervousness,  loss  of  flesh,  inter- 
mittent thyroid  hyperplasia,  palpitation  and  tachycardia,  etc.,  which 
would  incapacitate  her  for  months  at  a  time.  A  ventrofixation  of  the 
stomach  and  transverse  colon  performed  some  years  ago  cured  her  per- 
manently. That,  too,  was  a  fruste  form  of  hyperthyroidism,  secondary 
to  gastro-intestinal  auto-intoxication. 

There  are  fruste  forms  of  hyperthyroidism  in  which  besides  some 
insignificant  secondary  thyrotoxic  symptoms  the  only  marking  feature  is 
possibly  a  glycosuria  or  fatty  stools.  As  shown  by  Falta,  such  cases 
may  be,  too,  obscure  forms  of  hyperthyroidism  because  indirect  inter- 
vention upon  the  thyroid  by  operation  or  .x-rays  has  brought  about  cures. 

Fruste  forms  of  hyperthyroidism  are  observed,  too,  in  conjunction 
with  pelvic  diseases.  There,  too,  a  timely  operation  upon  the  diseased 
pelvic  organs  may  restore  the  patient  to  health. 

In  conclusion  we  may  say  that  these  fruste  forms  of  hyperthyroidism 
may  have  the  most  protean  character.  In  some  of  them  we  find  only 
thyroid  enlargement,  in  some  others,  tachycardia,  in  some  others  tremor, 
in  some  others  the  staring  and  glaring  look,  in  others  nervous  insta- 
bility, hot  flashes,  loss  of  flesh,  gastro-intestinal  disturbances,  psychic 
troubles,  etc.  A  great  many  of  these  cases  are  secondary  to  some  defi- 
nite pathological  condition.  For  a  great  many  others  there  seems  to 
be  no  apparent  cause. 

I  should  not  want  to  be  accused  of  chauvinism,  of  seeing  thyro- 
toxicosis everywhere.  Discretion,  judgment,  clinical  sense  must  be  our 
guide.  We  must  remember  that  "too  little,"  just  as  well  as  "too  much" 
always  spoils  everything,  or  as  the  French  say:  " Le  trop  et  le  trop  peu 
gdtent  tous  les  jeux." 


CHAPTER   XXXIV. 
HYPERTHYROIDISM  AND   HYPOTHYROIDISM. 

It  seems  at  first  nonsensical  to  claim  that  symptoms  of  thyroid  insuffi- 
ciency may  coexist  with  those  of  Graves'  disease,  in  short,  that  we  may 
have  at  the  same  time  hypothyroidism  and  hyperthyroidism;  yet  that 
there  can  be  such  a  thing  there  is  no  doubt.  The  thing  seems  at  first 
unacceptable  because  we  think  only  of  the  fully  developed  form  of  hypo- 
thyroidism. We  forget  that  until  the  condition  has  reached  its  full 
development  there  are  numbers  of  intermediary  stages,  in  short,  that 
we  have  fruste  forms  of  hypothyroidism  as  well  as  of  hyperthyroidism. 
No  one,  I  am  sure,  will  deny  that  a  given  case  of  Graves'  disease  may 
ultimately  turn  into  a  myxedematous  condition.  We  have  stated  more 
than  once  before  that  a  Basedow  patient,  provided  he  lives  long  enough 
and  the  thyrotoxic  process  keeps  up,  is  logically  destined  to  become  a 
myxedematous  case.  A  number  of  authenticated  cases  could  be  cited 
to  support  that  statement,  so  that  there  can  be  no  doubt  about  it.  For 
instance,  Joffroy  and  Achard  reported  the  case  of  a  young  woman, 
twenty-three  years  old,  who  had  a  typical  Basedow  and  who  finally 
developed  a  typical  cachexia  thyreopriva.  The  autopsy  showed  a  sar- 
coma of  the  pleural  cavity  and  a  more  or  less  complete  destruction  of 
the  thyroid  at  which  place  connective  tissue  only  was  to  be  found. 

How  shall  we  explain  the  combination  of  these  two  conditions  in 
Graves'  disease  ?  Because  there  the  gland  keeps  up  burning  at  a  fast 
pace.  This  obviously  cannot  last  forever.  There  comes  a  time  when 
the  gland  is  exhausted;  the  epithelial  elements  become  ''stale,"  undergo 
degeneration,  and  are  gradually  replaced  by  connective  tissue,  thus 
naturally  leading  into  hypofunction,  and  consequently  into  hypothy- 
roidism. Tachycardia,  nervousness,  tremor,  loss  of  flesh,  etc.,  gradually 
subside;  and  little  by  little  the  patient  sees  his  thyrotoxic  condition 
improve.  Everybody  thinks  the  cure  is  near.  But,  alas,  this  does  not 
last  long;  it  is  only  a  transitory  stage.  The  patient's  spirits  soon  become 
curbed,  his  eyes  lose  their  brilliancy  and  become  dull;  nervousness 
gradually  fades  away  into  quiet  and  rest,  the  intelligence  becomes  weak 
and  lazy,  tachycardia  gradually  subsides,  and  a  suspicious  adipose  tis- 
sue of  yellowish  tint  takes  the  place  of  the  previous  extreme  thinness  of 
the  skin.  The  patient  falls  into  a  state  of  marasmus.  Me  got  rid  of  his 
hyperthyroidism  only  to  fall  into  a  state  which  is  just  as  bad,  hypothy- 


364 


HYPERTHYROIDISM  AND  HYPOTHYROIDISM 


roidism.  He  saved  himself  from  Charybdis  only  to  fall  into  Scylla. 
Until,  however,  hypothyroidism  is  fully  developed,  symptoms  belong- 
ing to  both  conditions  remain  mixed  together.  Even  when  cachexia 
strumipriva  is  fully  developed,  there  still  remain  some  thyrotoxic  symp- 
toms which  will  show  that  both  conditions  may  exist  at  the  same  time 
in  the  same  patient.  The  case  is  an  odd  mixture  of  the  wreckage  of 
Graves'  disease  and  thyroid  insufficiency  (Fig.  69). 

As  a  rule  the  symptoms  of  hyperthyroidism  still  remain  the  pre- 
dominant ones;  only  a  few  isolated  symptoms  may  point  toward  hypo- 
thyroidism. For  instance,  the  patient  may  put  on  an  excessive  amount 
of  fat,  while  at  the  same  time  his  skin  becomes  dry  and  scaly.     In  some 

other  instances  his  mental  activity  be- 
comes dull,  the  memory  loses  its  reliability, 
the  patient  is  quiet,  the  movements  are 
slow;  in  short,  the  patient  develops  a  new 
condition  in  direct  contrast  to  the  pre- 
vious one  in  which  he  was  constantly 
nervous  and  agitated.  Yet  the  other 
thyrotoxic  symptoms  remain  the  same. 
The  whole  condition  may  show  periods 
of  improvement  and  exacerbation. 

The  reverse  may  be  true.  Some  thyro- 
toxic symptoms  may  occur  during  the 
course  of  the  cachexia  strumipriva;  this, 
however,  is  rare,  but  has  been  observed 
by  men  of  note,  as  Kocher,  for  instance. 
The  possibility  of  the  coexistence  of 
hypothyroidism  and  hyperthyroidism  will 
become  more  plausible  and  intelligible  if 
we  remember  that  a  gland  such  as  the 
thyroid  has  not  only  one  function,  but  many 
ot  them.  It  contains  a  number  of  lipoids,  each  one  of  them  having  a 
definite  action  on  the  metabolism.  We  have  already  stated  that  Isco- 
vesco  isolated  from  the  thyroid  several  lipoids,  each  one  affected  with 
different  properties.  One  of  them,  for  instance,  injected  into  animals 
causes  myxedema;  another,  exophthalmic  goiter,  another  had  a  marked 
influence  upon  the  ovaries,  and  so  on.  If  this  should  be  true,  and  should 
be  further  corroborated,  the  explanation  for  the  existence  of  hypothy- 
roidism and  hyperthyroidism  would  then  be  a  simple  one.  A  priori  at 
least,  according  to  all  that  we  know  of  the  glands  of  internal  secretion, 
these  findings  of  Iscovesco's  seem  rational.  We  know  that  adrenalin 
in  small  doses,  for  instance,  causes  vasodilatation,  and  in  large  doses, 
vasoconstriction. 


Fig.  69. — "Burned  out"  thyroid. 
Symptoms  of  hyper-  and  hypothy- 
roidism combined. 


CHAPTER  XXXV. 
INFANTILE  AND  JUVENILE   HYPERTHYROIDISM. 

As  we  have  an  infantile,  a  juvenile,  an  adolescent  and  an  adult 
hypothyroidism,  so  we  have  also  an  infantile,  a  juvenile,  an  adolescent, 
and  an  adult  hyperthyroidism. 

The  term  infantile  hyperthyroidism  is  intended  to  embrace  only  those 
cases  of  exophthalmic  goiter  occurring  in  children  before  ten  years  of 
age,  since  during  that  period  of  development  the  genital  system  is  still 
in  its  expectancy.  Juvenile  hyperthyroidism  is  that  form  of  thyrotoxi- 
cosis occurring  from  10  to  15  years  of  age,  during  which  period  the  geni- 
tal system  undergoes  its  development.  We  shall  call  adolescent  hyper- 
thyroidism the  cases  of  thyrotoxicosis  which  occur  from  fifteen  to 
twenty-five  years  of  age,  during  which  period  the  genital  apparatus 
reaches  its  maturity,  and  we  finally  reserve  the  term  adult  hyper- 
thyroidism, to  the  cases  occurring  after  twenty-five  years  of  age. 

Infantile  hyperthyroidism  is  comparatively  rare,  whereas  the  juvenile 
form  is  more  frequent.  W.  H.  Lewis,  quoting  Mayo's  statistics,  found 
one  case  of  infantile  hyperthyroidism  for  300  adult  cases  operated 
for  thyrotoxicosis.  The  youngest  of  his  cases  was  four  years  old  when 
it  came  under  his  observation,  and  the  disease  had  already  existed 
eighteen  months.  Infantile  and  juvenile  hyperthyroidism  follow,  as  a 
rule,  a  milder  and  shorter  course  than  that  of  adult  hyperthyroidism. 
Left  alone,  the  condition  gives,  according  to  Sattler,  a  mortality  of 
4.5  per  cent. 

The  symptoms  most  commonly  observed  in  infantile  hyperthyroid- 
ism are  irritability,  nervousness,  and  tachycardia.  The  little  patients 
seldom  are  conscious  of  palpitation;  exophthalmos  is  rarely  marked,  and 
the  ocular  symptoms  are  usually  absent.  Tremor  as  well  as  vasomotor)' 
disturbances  of  the  skin  are  present  in  moderate  degree.  Gastro- 
intestinal disturbances  are  usually  quite  marked.  As  a  rule  these 
young  patients  especially  those  of  infantile  type,  do  not  experience  the 
profound  muscular  asthenia  which  is  so  often  observed  in  adolescent  and 
adult  hyperthyroidism.  They  are  able  to  participate  in  the  activities 
of  their  young  companions  without  undue  fatigue.  Sometimes,  however, 
they  get  out  of  breath  more  easily.  Thyroid  hyperplasia  is  of  moderate 
degree  and   is  subject  to  variations.      Vascular  symptoms  are   present. 


366  INFANTILE  AND  JUVENILE  HYPERTHYROIDISM 

In  the  juvenile  and  adolescent  forms  of  hyperthyroidism  psychic  dis- 
turbances and  chorea  may  occur  as  complications.  Glycosuria  is  seldom 
observed. 

In  overactive  children  when  restlessness,  irritability,  egotism,  sel- 
fishness develop,  the  possibility  of  hyperthyroidism  should  always  be 
considered. 

So  far  as  treatment  is  concerned,  usually  ligation  of  both  superior 
poles  proves  of  itself  curative.  If  the  case  is  already  quite  markedly 
advanced,  thyroidectomy   may  become  necessary. 


CHAPTER  XXXVI. 
EXOPHTHALMIC  GOITER   IN   PREGNANCY. 

That  a  woman  afflicted  with  Graves'  disease  may  become  pregnant, 
or  that  thyrotoxicosis  may  develop  either  during  or  at  least  in  connec- 
tion with  pregnancy,  is  a  well-known  fact.  The  point  of  interest  does 
not  he  therein.  What  we  want  to  know  is,  how  do  these  two  conditions 
influence  each  other,  and  what  shall  be  our  attitude  in  these  given 
cases  ? 

The  coincidence  of  pregnancy  with  Basedow  is  not  frequent.  Out  of 
15,000  women  seen  in  the  Maternity  of  Edinburgh  by  Halliday-Croom, 
only  1  case  of  exophthalmic  goiter  in  pregnancy  was  seen.  The  other 
12  cases  which  he  reported  were  taken  from  his  private  practice,  hence 
his  conclusion  that  pregnane)*  and  Graves'  disease  are  oftener  found 
among  the  rich  classes  than  among  the  poor  ones.  Bonnaire  came  to 
the  same  conclusion,  because  out  of  30,000  pregnant  women  he  saw  only 
2  cases  of  exophthalmic  goiter. 

Seitz  has  collected  112  cases  of  exophthalmic  goiter  complicated 
with  pregnane}*  from  his  own  material,  from  literature,  and  from  circu- 
lar letters.  He  has  carefully  tabulated  the  menstrual  history,  the  appear- 
ance of  the  first  symptoms,  the  history  of  previous  pregnancies,  the 
therapy  employed,  and  the  results  as  far  as  mother  and  child  were  con- 
cerned. He  found  that  hyperthyroidism  was  not  affected  one  way  or 
the  other  in  40  per  cent,  of  the  cases.  A  very  small  number  even 
improved  during  pregnancy.  On  the  other  hand,  67  out  of  112  cases, 
namely,  60  per  cent,  of  the  total,  were  made  distinctly  worse  by  gesta- 
tion. In  one-fourth  of  these  67  patients  a  serious  menace  as  to  health 
and  life  was  the  consequence  of  thyrotoxicosis;  7  patients  died;  in  5 
cases  therapeutic  abortion,  and  in  1 1  cases,  premature  labor  occurred. 
Three  miscarriages,  and  3  macerated  fetuses  were  observed.  In  7  cases 
thyroidectomy  was  performed  during  pregnancy.  Bernard  von  Beck  in 
260  cases  of  Graves'  disease  and  pregnancy  said  that  he  felt  compelled 
to  perform  thyroidectomy  in  5  cases,  and  in  no  case  did  he  find  it  neces- 
sary to  interrupt  the  pregnancy.  As  Gellhorn  says,  this  is  indeed  a 
remarkable  record  and  may  be  explained  by  the  fact  that  these  thyro- 
toxic conditions  were  secondary  to  previous  existing  goiters,  since  in  the 
region  where  von  Beck  is  working,  goiter  is  endemic.  Theilhabei  found 
that  the  majority  of  coincident  cases  of  pregnancy  and  Graves'  disease 
were  made  distinctly  worse  by  the  disease  and  that  only  the  minority 


368        EXOPHTHALMIC  GOITER  IN  PREGNANCY 

were  improved  by  it.  Kleinwachter  and  Hirst  came  to  the  same  conclu- 
sion that  Graves'  disease  is  unfavorably  influenced  by  pregnancy,  and 
that  it  often  has  its  origin  in  gestation.  It  predisposes  the  patients  to 
uterine  hemorrhages  and  may  result  in  the  death  of  the  fetus.  Such 
cases  are  often  complicated  with  albuminuria.  Whitridge  Williams  con- 
siders that  pregnancy  exerts  a  deleterious  influence  on  Graves'  disease; 
he  found  that  tachycardia  was  greatly  increased  during  gestation  and 
lessened  soon  after  labor.  It  has  been,  too,  my  experience  in  the  cases 
of  thyrotoxic  pregnant  women  I  have  seen. 

We  can  consequently  conclude  that  the  majority  of  Graves'  patients 
are  made  worse  by  pregnancy.  Pregnancy  must  be  regarded  as  a  serious 
complication  in  thyrotoxicosis.  This  is  so  true  that  Theilhaber  has  said 
when  speaking  of  thyrotoxic  patients: 

"Girls,  no  marriage;  women,  no  pregnancy;  mothers,  no  nursing." 

Treatment. — So  far  as  Graves'  disease  is  concerned,  medical  treat- 
ment should  be  given  the  greatest  care  and  attention  as  soon  as  preg- 
nancy is  detected.  Every  form  of  treatment  can  be  given  a  trial.  Opo- 
therapy with  hypophysis,  or  with  thymus  may  be  attempted;  opother- 
apy with  thyroid  should  be  handled  with  extreme  care.  Any  one  of 
these  treatments  will  sometimes  give  good  results,  more  often  none,  or 
it  will  make  the  condition  of  the  patient  worse.  Up  to  date  the  best 
treatment  known  is  a  dietetic,  hygienic  regime.  The  majority  of  cases 
so  treated  will  be  kept  in  fairly  good  condition  and  may  be  brought 
along  to  the  full  term  of  their  pregnancy  without  too  serious  disturbances. 
At  any  rate,  during  the  early  period  of  pregnancy  the  treatment  must 
be  a  watchful,  waiting  one.  If  later,  however,  the  condition  of  the  patient 
grows  worse,  surgical  intervention  then  becomes  necessary. 

Surgically,  two  questions  arise:  Shall  we  perform  a  thyroidectomy  or 
shall  we  resort  to  an  obstetrical  operation  ?  So  far  the  trend  of  opin- 
ion seems  to  be  in  favor  of  the  second  alternative.  If  the  fetus  is  viable, 
a  premature  Cesarean  section  may  save  its  life,  which  very  likely  would 
be  lost  if  allowed  to  go  on  to  full  term.  If,  on  the  other  hand,  the  fetus 
is  not  viable  and  the  condition  of  the  mother  is  such  as  to  necessitate  a 
surgical  intervention,  the  life  of  the  child  should  be  sacrificed  without 
hesitation,  since  at  any  rate  it  is  bound  to  be  lost.  In  such  cases  the 
mother's  life  only  should  be  taken  into  consideration. 

I  believe,  however,  that  we  should  not  wait  until  these  thyrotoxic 
symptoms  complicated  with  pregnancy  have  become  so  serious  as  to 
endanger  the  life  of  both  the  mother  and  the  child.  A  timely  thyroid- 
ectomy as  I  have  performed  twice  seems  to  be  the  ideal  procedure,  as  it 
not  only  wonderfully  benefits  the  thyrotoxic  condition,  but  also  allows 
the  pregnancy  to  go  to  full  term,  and  thus  saves  the  life  of  the  child 
without  undue  risks  for  the  mother. 


TREATMENT  369 

Basedow  patients  should  be  guarded  against  marriage,  and  espe- 
cially against  pregnane)'.  At  any  rate,  before  entering  married  life  they 
should  have  thyroidectomy  performed  in  order  to  safeguard  them  against 
any  future  exacerbations  and  to  protect  their  future  offspring.  It  is 
true  that  in  severe  forms  of  Graves'  disease  the  chances  for  pregnancy 
are  considerably  reduced,  because  the  sexual  apparatus  is  in  a  state  of 
hypofunction.  This,  however,  is  not  always  the  case  and  pregnancies 
may  occur  even  in  very  severe  cases  of  thyrotoxicosis.  When  this  is 
the  case  "sterilization"  of  the  women  should  be  performed  after 
pregnancy  is  over. 


24 


CHAPTER  XXXVII. 
ETIOLOGY  OF   GRAVES'  DISEASE. 

The  fact  that  Filehnes,  Walburton,  Tedeschi,  Dourdoufi,  and 
Bienfait  by  sectioning  the  restiform  bodies  were  able  to  produce  tachy- 
cardia, exophthalmos,  hyperemia  of  the  thyroid,  etc.,  has  given  rise  to 
a  theory  claiming  that  Basedow's  disease  is  of  bulbar  origin.  It  must  be 
said,  however — and  this  is  a  very  important  point  to  remember — that 
the  thyrotoxic,  clinical  picture  did  not  take  place,  if  previously  or  at 
the  same  time,  thyroidectomy  had  been  performed.  The  French  school, 
especially  Charcot,  Trousseau,  etc.,  and  the  German  school,  represented 
by  Gerhardt,  Buscham,  Wickfield,  Sattler,  etc.,  have  considered  Base- 
dow's disease  as  a  neurosis  of  the  entire  vegetative  nervous  system. 
Notkine  and  Blum  defended  the  view  that  Basedow's  disease  was  due  to 
an  insufficient  "depoisoning"  of  the  organism  by  the  thyroid  on  account 
of  functional  insufficiency.  Friedreich  considered  Basedow's  disease  as 
due  to  an  abnormal  enlargement  of  the  coronary  arteries  of  the  heart, 
thus  causing  an  increased  blood  supply  to  the  cardiac  muscle  which  in 
turn  would  cause  an  increased  excitability  of  the  nervous  system.  Gabriel 
Gauthier  considered  the  thyrotoxic  syndrome  as  of  thyroid  origin. 
Mannheim  considered  it  as  of  central  origin.  Moebius  claimed  that 
Basedow  was  caused  by  poisoning  of  the  blood  by  the  thyroid  products, 
and  considered  the  forms  frustes  as  well  as  the  primary  and  secondary 
forms  of  exophthalmic  goiter  as  all  produced  by  the  same  cause,  namely, 
the  hyperfunction  of  the  thyroid.  Crile  believes  that  it  is  a  "philo- 
genic"  disease,  caused  by  a  disturbance  of  the  entire  motor  mechanism 
in  which  the  nervous  system  is  primarily  involved  and  in  which  the  thy- 
roid acts  as  an  activator.  Hart  and  Bircher  believe  that  Basedow's  dis- 
ease is  primarily  of  thymic  origin.  Klose,  Lampe,  and  Liesegang  believe 
that  the  disease  is  due  to  dysthyroidism.  Thus,  as  one  can  see,  the 
theories  concerning  the  etiology  of  Graves'  disease  are  numerous,  and  I 
have  not  cited  them  all  by  any  means. 

The  theory  which  up  to  date  has  rallied  the  greatest  number  of  parti- 
sans is  the  theory  of  hypersecretion  of  Moebius,  called  thyrotoxicosis  by 
Kocher,  and  hyperthyroidism  by  Mayo.  According  to  these  authors, 
Basedow's  disease  is  caused  by  a  surplus  of  thyroid  secretion  poisoning 
the  entire  organism.  This  surplus  may  be  caused  either  by  an  increased 
function  of  the  thyroid  or  by  thyroid  feeding.    This  theory  is  indeed  the 


ETIOLOGY  OF  GRAVES'  DISEASE  371 

one  which  tallies  best  with  our  present  knowledge,  and  which  seems  to 
be  best  supported  by  the  facts.  It  is  simple  and  clear,  but  I  am  afraid 
that  just  because  of  this  simplicity  and  clearness,  it  is  insufficient.  The 
more  one  studies  this  question,  the  more  one  becomes  convinced  that 
the  problem  is  a  complicated  one;  the  more  one  tries  to  penetrate  the 
secrets  of  Nature,  the  more  one  sees  how  intricate  her  wars  are.  As 
v.  Hansemann  says,  "Nature  does  not  know  a  cause,  but  causes." 
Indeed,  if  we  consider  an  event  in  its  simplest  form,  even  though  the 
determining  factor  seems  to  be  obvious,  how  many  other  "preparatory" 
conditions  are  not  necessary  to  allow  the  so-called  primary  cause  to 
exert  its  effect  ?  And  so  it  is  in  medicine.  Almost  everyone  will  say,  for 
instance,  that  tubercle  bacilli  are  the  cause  of  tuberculosis,  yet,  if  truly 
they  were  the  only  cause,  every  living  man  would  be  tuberculous  because 
it  has  been  shown  beyond  doubt  that  everybody's  organism  contains 
tubercle  bacilli.  Fortunately,  in  order  to  allow  tubercle  bacilli  to  thrive, 
other  "preparatory  conditions"  are  just  as  necessary  as  the  presence 
of  the  tubercle  bacilli  themselves,  and  only  when  all  these  conditions 
happen  to  be  assembled,  does  tuberculosis  develop.  It  is  consequently 
wrong  to  say  that  tubercle  bacilli  are  solely  the  cause  of  tuberculosis. 
One  should  say  "tubercle  bacilli  are  one  among  others  of  the  conditions 
necessary  for  the  development  of  tuberculosis."  If  one  of  these  "con- 
ditions" is  absent,  there  will  be  no  tuberculosis.  Take,  for  example, 
Addison's  disease.  If  tubercle  bacilli  were  the  only  necessary  require- 
ment, again,  almost  everybody  would  have  Addison's  disease.  This 
disease  is  too  fairly  frequent  to  be  considered  as  the  result  of  the  mere 
accidental  settling  of  tubercles  in  the  suprarenal  bodies;  furthermore,  the 
fact  that  the  tuberculous  involvement  is  bilateral,  speaks,  too,  against 
such  an  explanation.  The  truth  of  the  matter  is  that  other  conditions, 
secondary  indeed,  but  just  as  necessary  and  important  as  the  tubercle 
bacilli,  must  intervene  before  the  invading  tubercle  bacilli  can  thrive  in 
the  suprarenal  bodies.  Exceedingly  forceful  in  demonstrating  this  very 
thing  is  the  hypothetical  example  mentioned  by  Sahli,  that  of  a  child 
who  has  been  slapped  in  the  face  once  by  its  teacher,  and  who  develops 
soon  after  a  tubercular  meningitis.  At  once  the  family  concludes  that 
the  slap  in  the  face  was  the  cause  of  the  tubercular  meningitis,  hence 
a  lawsuit  for  damages.  "This  lawsuit,"  says  the  defendant,  "is  ridicu- 
lous. Everybody  knows  that  without  tubercle  bacilli,  there  is  no 
tuberculosis,  that  if  a  tubercular  meningitis  develops,  the  child  must 
have  had  tubercle  bacilli  in  his  organism  previous  to  the  slap  in  the 
face,  that  slaps  in  the  face  are  given  every  day  without  there  occurring 
a  tubercular  meningitis,  that  finally  there  is  no  more  relation  between 
a  slap  m  the  face  and  tubercular  meningitis  than  then-  is  between  a 
belly-ache  and  tin-  moon."    "All  this  may  be  very  well,"  says  the  plain- 


372  ETIOLOGY  OF  GRAVES'  DISEASE 

tiff,  "but  the  fact  remains  that  the  child  was  well  before,  that  he  got 
sick  soon  after  the  slap  in  the  face,  consequently  had  he  not  been  slapped 
in  the  face,  he  would  not  have  developed  a  tubercular  meningitis." 
And  no  one  will  be  able  to  convince  the  plaintiff  to  the  contrary.  He 
sees  one  cause:  this  cause  suffices  to  explain  the  whole  thing.  He  does 
not  see,  or  does  not  want  to  see,  that  besides  this  apparent  cause  there 
are  many  others,  in  fact,  more  important,  without  which  a  tubercular 
meningitis  would  never  have  developed,  and  that  in  this  particular  case 
the  slap  in  the  face  was  merely  a  coincidence. 

And  so  it  is  for  the  etiology  of  Graves'  disease.  Of  course  the  thy- 
roid lesions  still  play  the  predominating  role  in  the  development  of  the 
disease.  But  this  is  not  all;  other  conditions  intervene;  other  factors 
play  their  part  too,  such  as  the  nervous  system,  and  the  organs  of 
internal  secretion.  It  is  for  this  reason  that  I  shall  say  that  Graves' 
disease  is  a  thyroneuropoly glandular  disease. 

Let  us  proceed  to  try  to  demonstrate  successively  and  separately 
the  three  members  of  that  proposition: 

A,  The  thyroid  origin. 

B,  The  nervous  origin. 

C,  The  polyglandular  origin. 

A.  Thyrogenetic  Origin  of  Graves'  Disease. — Arguments  in  favor  of 
the  thyrogenetic  origin  of  Graves'  disease  are  among  the  most  numerous; 
they  are  derived  from  clinical  observation,  from  pathology,  from  experi- 
mentation, and  from  the  results  of  surgical  treatment. 

i.  It  was  because  he  was  struck  by  the  antithesis  which  existed 
between  the  clinical  symptoms  observed  in  thyroid  insufficiency  and 
those  seen  in  Graves'  disease  that  Moebius  concluded  that  the  latter 
condition  was  due  to  a  hyperfunction  of  the  thyroid.  Indeed,  one 
cannot  but  be  impressed  in  the  same  way  after  glancing  over  the 
masterful  synopsis  made  by  Kocher  in  1902.  It  takes  the  two 
opposite   conditions  at  their  worst,  and   reads  as  follows: 

Hypothyroidism.  Hyperthyroidism. 

Absence  or  atrophy  of  the  thyroid  gland.         Diffuse      hyperplasia      of     the      thyroid. 

Hypervasculanzation. 
Slow,  regular  pulse  of  small  volume.  Rapid    pulse,    rather    increased    pressure, 

sometimes  irregular. 
Absence  of  hot  flashes,  se  nsation  of  cold.         Marked  vasomotory  disturbances.    Patient 

is  always  too  warm. 
Indifferent,     expressionless     and      lifeless         Very    anxious,    exceedingly    mobile    look 

look.  with    a   rapidly   changing   expression. 

Small   palpebral   fissure,    small   eyes.  Wide  palpebral  fissure  and  exophthalmos. 

Bad  appetite,  slow  digestion,  constipation.         Often  increased  appetite,  vomiting,   diar- 


rh 


ea. 


THYROGEXETIC  ORIGIN  OF  GRAVES'  DISEASE 


373 


Hypothyroidism. 

Reduced  metabolism. 

Thick,  cold,  dry,  scaling  skin. 

Short,  thick  fingers  with  thickened  ter- 
minal phalanges. 

Great  tendency  to  sleep. 

Reduced  sensibilitv  and  diminished  sen- 
sory impressions. 

Diminished  mental  and  intellectual  power. 


Awkwardness  and  slow  actions. 
Stiffness  of  the  extremities. 
Short,  thick,  often  deformed  skeleton. 
Slow,  deep,  respiration. 

Increase  in  weight. 

Old     appearance    of    the     patient,     even 
though    young    in    years. 


Hyperthyroidism. 

Increased  metabolism. 

Thin,  warm,  soft,  moist  skin,  no  scaling. 

Long,  thin  fingers  with  pointed  phalanges. 

Insomnia  and  disturbed  sleep. 

Increased  sensibility  and  increased  sen- 
sory impressions. 

Increased  mental  and  intellectual  activity, 
great  psychic  excitement,  hallucina- 
tions,   mama,    and    melancholia. 

Restlessness   and    haste   in    movements. 

Tremor  but  marked  agility  in  movements. 

I  hin,  slender  skeleton. 

Superficial,  rapid,  and  slightly  irregular 
respiration. 

Loss  of  weight. 

Rather  youthful  appearance,  especially 
in  the  early  stage  of  the  disease. 


Furthermore,  Kocher  found  that  phosphates  are  beneficial  to  hyper- 
thyroidism, but  are  harmful  to  hypothyroidism;  that  a  sojourn  in  high, 
cold  climates  is  beneficial  to  hyperthyroidism,  but  harmful  to  hypo- 
thyroidism; that  a  sojourn  at  the  sea  is  harmful  to  hyperthyroidism, 
but  helpful  to  hypothyroidism.  Certainly  the  antithesis  between  all 
these  symptoms  is  forceful  and  speaks  strikingly  not  only  in  favor 
of  the  thyrogenetic  origin  of  the  disease,  but  also  in  favor  of  the 
hyperthyroidism  theory. 

2.  The  fact  that  thyroid  feeding  is  most  injurious  to  the  great  majority 
of  cases  of  Graves'  disease,  and  produces,  as  a  rule,  only  exacerbation 
of  all  the  symptoms,  must  be  interpreted  as  another  proof  of  the  thyro- 
genetic origin  of  Graves'  disease,  and  of  the  hyperthyroidism  theory. 
Since  in  hypothyroidism  the  feeding  of  thyroid  extract  is  curative,  it 
is  logical  to  consider  the  bad  results  obtained  from  thyroid  feeding  in 
Graves'  disease  as  directly  due  to  the  increased  amount  of  thyroid  secre- 
tion in  an   already  saturated  organism. 

3.  In  cases  where  thyroidectomy  has  been  performed  in  view  of 
remedying  the  thyrotoxic  condition,  if  a  relapse  of  symptoms  occurs, 
there  is,  too,  a  relapse  of  the  goiter,  and  vice  versa;  hence  another 
proof  in  favor  of  the  intimate  relation  of  the  goiter  with  the  clinical 
symptoms  of  the  disease. 

4.  Another  powerful  argument  is  derived  from  the  clinical  observa- 
tion that  in  many  cases  of  secondary  thyrotoxic  goiters  one  can  follow 
a  gradual  transition  in  the  intensity  of  the  symptoms  going  from  the 
slightest  form  of  thyrotoxicosis  to  the  most  fully  developed  picture  of 
Graves'  disease.     Anyone  who  has  had   experience   with  goiters  knows 


374  ETIOLOGY  OF  GRAVES'  DISEASE 

that  this  sliding  of  the  scale  is  quite  frequent.  As  Wolfler  says,  "It  is 
easy  to  go  progressively  from  a  simple  goiter  to  a  well-marked  case  of 
Graves'  disease,  as  for  instance,  goiter  with  tachycardia;  goiter  with 
tachycardia  and  tremor;  goiter  with  tachycardia,  tremor,  and  exoph- 
thalmos; goiter  with  tachycardia,  tremor,  exophthalmos,  and  digestive 
disturbances,  etc.,  until  we  get  the  complete  clinical  picture  of  Basedow's 
disease."  These  cases,  no  matter  if  they  are  fully  developed,  or  consti- 
tute only  the  fruste  forms  of  Graves'  disease,  all  recognize  the  same 
etiology;  they  are  all  dependent  upon  the  thyroid  intoxication. 

5.  Another  proof  in  favor  of  the  hyperfunction  of  the  thyroid  is  the 
fact  that  exophthalmic  goiter  seldom  occurs  in  regions  where  goiter 
is  endemic,  namely,  where  the  thyroid  is  permanently  and  endemically 
in  a  state  of  hypofunction.  Even  when  such  endemic  goiters  become 
overactive,  the  worst  they  can  do  is  to  give  birth  to  mitigated  forms  of 
hyperthyroidism  such  as  thyrotoxic  goiter-heart,  nervousness,  etc. 
They  seldom  reach  the  fully  developed  thyrotoxic  clinical  picture.  As 
soon,  however,  as  we  consider  regions  where  goiter  is  not  endemic  or 
mildly  so,  where  consequently  the  thyroid  gland  has  retained  its  full 
functional  capacity,  there  Basedow  disease  becomes  very  frequent  and 
severe  in  its  forms. 

6.  If  in  order  to  obtain  shrinkage  of  the  gland,  the  thyroid  is  attached 
to  the  integuments  by  the  operative  measure  known  as  exothyropexy, 
it  is  found  that  the  thyrotoxic  goiters  show  a  far  greater  secretion  than 
the  simple  goiter,  hence  the  conclusion  that  the  thyrotoxic  goiter  func- 
tionates more  than  the  simple  one  is  obvious. 

7.  The  fact,  on  the  one  hand,  that  a  sudden  hemorrhage  occurring 
in  an  already  existing  colloid  or  cystic  goiter  will  cause  marked  thyro- 
toxic symptoms,  such  as  palpitation,  great  nervousness,  tremor,  gastro- 
intestinal disturbances,  insomnia,  and  even  sometimes  a  moderate  exoph- 
thalmos; and,  on  the  other  hand,  the  fact  that  all  these  symptoms  will 
subside,  as  resorption  of  the  hemorrhage  goes  on,  and  will  finally  dis- 
appear when  the  goiter  has  returned  to  its  quiescent  state  again,  or  on 
the  contrary,  will  increase  progressively  into  a  true  case  of  Basedow's 
disease  when  the  thyroid  does  not  quiet  down,  all  go  to  show  that  there 
is  a  relation  from  cause  to  effect  between  the  pathology  of  the  thyroid 
and  Graves'  disease. 

8.  The  fact  that  Basedow's  disease  is  found  with  an  acute  thyroiditis 
is  another  proof  of  the  thyrogenetic  origin  of  Graves'  disease.  This 
question  will  be  discussed  later  in  considering  the  relation  between 
thyroiditis  and  Graves'  disease. 

9.  The  coexistence  of  thyrotoxic  symptoms  with  malignant  goiter 
has  long  since  been  known.  Already  in  1871  Tillaux  mistook  a  sarcoma 
of  the  thyroid  for  an  exophthalmic  goiter.     Carrel,  out  of  83  malignant 


PATHOLOGICAL  ARGUMENTS  375 

goiters  found  26  showing  unmistakable  thyrotoxic  symptoms.  Poncet 
and  Bouveret  saw  a  malignant  goiter  with  a  complete  clinical  picture 
of  Basedow's  disease,  exophthalmos  included.  Delore  and  Alamartine, 
Kocher,  and  myself  have  seen  similar  cases. 

The  thyrotoxic  symptoms  occur  either  after  metastases  have  taken 
place  or  before.  If  they  occur  only  after  the  tumor  has  metastasized, 
since  we  know  that  malignant  metastases  of  thyroid  tissue  always  retain 
their  physiological  secreting  power,  then  it  is  logical  to  conclude  that 
the  symptoms  of  hyperthyroidism  are  due  to  the  increased  functionating 
surface  due  to  the  malignant  tumor  plus  its  metastases.  If  thyrotoxic 
symptoms  occur  before  metastases  have  taken  place,  the  hyperfunction 
may  be  due  to  the  fact  that  the  malignant  portions  of  the  tumor  irritate 
the  remaining  normal  glandular  tissues  and  incite  it  to  hyperplasia  in 
the  same  way  that  intraglandular  hemorrhage  does:  hence  symptoms 
of  hyperthyroidism  as  we  see  them  sometimes  after  hemorrhage  in  simple 
non-toxic,  cystic,  or  colloid  goiters. 

Pathological  Arguments. — It  is  not  enough  to  support  our  conclusions 
with  clinical  data.  No  matter  how  strong  these  clinical  proofs  may  be, 
they  alone  would  not  carry  conviction  as  well  as  the}"  would  if  they 
were  supported  by  convincing  pathological  evidence.  Let  us  see  what 
pathology  teaches  us. 

We  have  seen  in  the  Chapter  dedicated  to  Basedow  Struma  that  hyper- 
plasia of  the  thyroid  is  one  of  the  most  constant  findings  in  thyrotoxi- 
cosis, so  constant  that  Kocher  has  said,  ''No  goiter,  no  Graves'  disease." 
It  is  indeed  true  that  in  the  great  majority  of  cases  an  enlargement  of 
the  thyroid  is  present.  As  a  rule  it  is  obvious.  It  would  be  a  mistake, 
however,  to  believe  that  thyrotoxicosis  necessarily  means  that  thyroid 
hypertrophy  is  always  clinically  detectable.  There  are  cases  of  thyro- 
toxicosis, even  very  severe  ones,  with  only  a  slight  hyperplasia  or  none 
at  all.  In  a  great  many  cases,  this  hyperplasia,  which  is  clinically 
"apparently"  absent,  is  nevertheless  present.  This  is  proved  time  and 
time  again  because  at  the  time  of  the  operation  the  gland  is  found  to 
be  larger  than  normally.  Furthermore,  it  must  not  be  forgotten  that 
hyperplasia  of  the  thyroid  in  Basedow  fluctuates  with  the  stage  of  the 
disease  itself,  that  the  time  when  the  patient  comes  for  examination  may 
be  very  well  the  period  in  which  hyperplasia  is  in  its  incipient  stage,  or 
in  which  the  thyroid  has  returned  to  its  quiescent  state,  or  is  undergoing 
atrophy:  hence  the  impression  then  that  there  is  no  enlargement  ot  the 
thyroid.  If,  however,  a  careful  history  is  taken,  one  will  almost  always 
learn  that  at  one  time  or  another  there  was  some  enlargement.  So  far, 
so  good.  But  there  is  better.  We  have  seen  that  the  microscopic 
changes  in  the  gland  are  characteristic  of  Graves'  disease;  and  that 
hypertrophy  and  hyperplasia  of  the  cellular  elements,  thinning  ot  the 


371)  ETIOLOGY  OF  GRAVES'  DISEASE 

colloid,  more  or  less  marked  desquamation  and  cytolysis,  and  the  pres- 
ence of  foci  of  lymphoid  tissue  throughout  the  parenchyma  are  its  chief 
characteristics.  These  changes  have  been  found  by  such  a  great  number 
of  authors  that  they  certainly  cannot  be  considered  as  merely  accidental; 
they  must  bear  a  direct  relation  to  the  clinical  syndrome  of  Graves' 
disease.  Before  we  have  the  right,  however,  to  consider  these  histological 
changes  as  specific  for  Graves'  disease,  we  should  prove  that  these  changes 
occur:  (i)  constantly  in  that  condition;  (2)  that  they  occur  in  no  other 
condition  but  Graves'  disease.  So  far  as  the  first  condition  is  concerned, 
we  have  concluded  with  L.  B.  Wilson  (loc.  cit.) :  "By  assuming  that 
the  symptoms  of  the  true  exophthalmic  goiter  are  the  results  of  an  excre- 
tion from  the  thyroid,  and  by  attempting  to  determine  the  amount  of 
such  excretion  from  the  pathological  data,  one  is  able  to  estimate  in  a 
large  series  of  cases  the  clinical  stage  of  the  disease  with  about  80  per  cent, 
of  accuracy,  and  the  clinical  severity  of  the  disease  with  about  75  per 
cent,  of  accuracy.  It  would  therefore  appear  that  the  relationship  of 
primary  hypertrophy  and  hyperplasia  of  the  parenchyma  of  the  thyroid 
to  true  exophthalmic  goiter  is  as  direct  and  constant  as  is  primary 
inflammation  of  the  kidney  to  the  symptoms  of  Blight's  disease.  Any 
considerable  finding  to  the  contrary  I  believe  to  indicate  either  inaccurate 
or  incomplete  observations  on  the  part  of  the  pathologist  or  clinician, 
or  both." 

We  have  further  seen  that  even  if  there  is  no  appreciable  macroscopic 
hypertrophy  of  the  gland,  these  typical  histological  changes  just  spoken 
of  could  be  found  either  diffusely  distributed  throughout  the  parenchyma 
or  in  the  isolated  areas,  provided  one  takes  the  trouble  to  make  seriated 
slides.  The  few  rare  cases  of  thyrotoxicosis  where  no  histological  changes 
are  present,  must  most  likely  depend  upon  the  disturbance  of  some  other 
organs  of  internal  secretion,  as  the  thymus,  for  instance. 

So  far  as  the  second  proposition  is  concerned,  we  must  admit,  too, 
that  similar  histological  changes  may  once  in  a  while  be  met  outside 
of  thyrotoxicosis  in  the  form  of  adenomatous  formations.  But  we  must 
not  forget  that  similar  does  not  mean  identical,  and  that  it  is  by  no  means 
certain  that  the  function  of  such  adenomatous  formations  as  are  some- 
times seen  in  non-toxic  conditions  is  identical  with  that  one  of  the 
hyperplastic  epithelium  seen  in  thyrotoxicosis.  Even  suppose  that  it 
were,  then  it  very  likely  constitutes  only  one  of  the  many  "preparatory 
conditions"  without  which  the  disease  cannot  develop,  as  it  requires 
more  than  the  mere  presence  of  the  tubercle  bacilli  to  cause  tuberculosis. 

On  the  whole,  we  can  consequently  admit  that  these  anatomical 
changes  in  the  thyroid  are  specific  of  the  disease. 

Experimental  Arguments. — Experimentation,  too,  has  furnished  its 
contingency   of  proofs   in   favor  of  the   thyrogenetic  origin   of  Graves' 


EXPERIMENTAL  ARGUMENTS  377 

disease.  Although  a  number  of  attempts  to  reproduce  experimentally 
in  animals  the  clinical  syndrome  of  Graves'  disease  have  proved  failures, 
nevertheless,  a  great  many  other  investigators,  whose  authority  and 
scientific  honesty  cannot  be  questioned,  have  succeeded  where  others 
have  failed.    The  doubt  as  to  the  feasibility  is  no  longer  permissible. 

Injected  subcutaneously  or  given  by  mouth,  thyroid  extracts  have 
more  or  less  the  same  influence  on  thyroidectomized  animals:  trophic 
disturbances  gradually  disappear,  myxedema  becomes  less  marked,  the 
skeleton  grows  again,  metabolism  increases,  the  blood  formula  reverts 
to  its  normal  type,  and  in  short,  the  animal  gradually  becomes  normal. 
This  thyroid  opotherapy  is  not  only  beneficial,  but  is  also  necessary 
because  if  it  is  not  kept  up,  the  animal  sinks  again  into  its  previous 
myxedematous  condition.  On  the  other  hand,  fed  to  normal  animals  in 
overdoses  or  for  too  long  a  period  of  time,  the  thyroid  extract  becomes 
harmful.  Tachycardia,  tremor,  dyspnea,  extreme  agitation,  brilliancy 
of  the  eyes,  fever,  polyuria,  and  in  many  instances,  exophthalmos  are 
the  results.  Why  such  a  difference  ?  Because  to  the  first  series  of  animals 
we  have  given  them  something  they  had  not,  something  they  needed. 
To  the  second,  we  have  added  a  surplus  of  thyroid  product  when  they 
already  had  plenty  of  it;  we  have  saturated  their  organism  with  it,  and 
it  is  that  surplus  which  has  become  injurious.  Experiments  proving 
such  contention  are  numerous.  Not  only  can  we  reproduce  the  whole 
clinical  syndrome,  but  also  the  characteristic  changes  in  the  blood, 
such  as  leukopenia,  hyperlymphocytosis,  hyperpolynucleosis,  diminished 
viscosity  and  coagulability  of  the  blood,  etc.  Ballet  and  Enriquez 
have  obtained  the  thyrotoxic  syndrome  accompanied  by  exophthalmos, 
after  daily  intravenous  injection  of  thyroid  products  into  animals. 
Krauss  and  Friedenthal,  injecting  intravenously  into  rabbits  the  thyroid 
products  dissolved  in  salt  solution,  observed  the  thyrotoxic  symptoms 
characterized  by  rapid  pulse,  nervousness,  tremor,  exophthalmos, 
widening  of  the  palpebral  fissure,  and  dilatation  of  the  pupils.  Tedeschi 
obtained  in  dogs  the  complete  clinical  picture  of  Basedow's  disease, 
namely,  tachycardia,  exophthalmos,  and  goiter  by  the  same  process. 
Cunningham  and  Hoennicke,  experimenting  upon  rabbits,  and  Edmunds, 
upon  a  monkey  and  dogs,  have,  too,  reproduced  the  clinical  syndrome 
of  Graves'  disease  with  exophthalmos.  Baruch,  in  191 2,  used  for  his 
experiments  non-toxic  parenchymatous  and  colloid  goiters.  Soon  after 
removal  these  goiters  were  ground  finely  so  that  they  could  be  injected 
subcutaneously  or  into  the  peritoneal  cavity.  With  this  method  he  repro- 
duced experimentally  in  dogs,  rabbits,  rats,  a  typical  Basedow's  disease 
characterized  by  nervousness,  emaciation,  loss  of  hair,  diarrhea,  tachy- 
cardia, glycosuria,  typical  blood  changes,  and  in  a  tew  instances  marked 
exophthalmos.     Three  of  such  dogs  with  exophthalmos  were  shown  by 


378  ETIOLOGY  OF  GRAVES'  DISEASE 

him  before  the  Breslau  Surgical  Society.  One  of  these  dogs  as  the  result 
of  lagophthalmos  developed  an  ulcer  of  the  cornea. 

Luthi  and  Verebeli,  after  producing  artificially  a  congestion  of  the 
thyroid  gland,  were  able  to  observe  in  the  thyroid  the  typical  histological 
changes  which  are  so  characteristic  of  Graves'  disease.  They  observed 
at  the  same  time  tachycardia  and  an  increased  excretion  of  nitrogen 
and  phosphorus. 

But  the  experiments  carrying  with  them  the  greatest  conviction  were 
undertaken  by  Klose  in  1909.  Convinced  that  the  unsuccessful  attempts 
made  by  others  to  obtain  the  fully  developed  clinical  symptoms  of  Graves' 
disease  were  due  to  the  fact  that  dried  and  powdered  gland  had  been 
used,  which  had  most  probably  lost  many  of  its  properties,  he  used  the 
thyrotoxic  goiters  in  their  fresh  state  as  soon  as  they  were  removed 
surgically  from  patients.  These  glands  were  submitted  to  a  squeezing 
process  and  the  juice  so  obtained,  called  Press-saft  or  "  Pressed  juice" 
was  then  injected  into  the  jugular  vein  of  dogs  and  without  anesthetic. 
Klose  found  that  the  best  results  were  obtained  whenever  he  used  "highly 
nervous  fox  terriers."  Soon  after  the  intravenous  injection  the  blood- 
pressure  sank  from  100  to  85  millimeters  of  mercury.  The  tachycardia 
became  exceedingly  marked,  pulse  was  at  times  scarcely  countable, 
respiration  became  irregular,  tremor,  sweating,  gastro-intestinal  disturb- 
ances were  very  pronounced,  fever  rose  high,  and  exophthalmos  in  many 
instances  became  very  apparent.  Albumin  and  sugar  were  found.  The 
typical  blood  changes  were  present.  This  condition  lasted  for  a  few  days, 
then  subsided  and  the  dogs  became  normal  again.  These  experiments 
undertaken  on  a  large  number  of  dogs  always  showed  the  same  constant 
results.  The  intensity  of  the  symptoms  observed  was  dependent  upon 
the  toxicity  of  the  Press-saft  as  shown  by  the  clinical  symptoms:  the  most 
intense  toxic  symptoms  were  produced  by  the  Press-saft  from  primary 
thyrotoxic  goiters.  The  secondary  forms  or  Basedowified  goiters  were 
less  toxic.  The  toxicity  of  this  Press-saft  gradually  diminished  after 
standing,  and  after  a  period  of  five  or  six  days  became  powerless. 
Mechanical  shaking,  drying  of  the  gland,  heating  of  the  juice,  destroyed 
very  quickly  its  toxicity.  If  to  a  normal  thyroid  or  goiter  which  proved 
itself  non-toxic,  a  solution  of  iodide  of  potash  was  added,  the  toxicity  of 
the  Press-saft  at  once  became  apparent,  lasted  for  a  few  days  and  then 
disappeared.  In  injecting  enormous  doses  of  Press-saft  from  non-toxic 
goiters  or  from  other  organs  such  as  the  liver,  etc.,  Klose  was  unable  to 
obtain  the  Basedow  symptoms. 

Efforts,  although  few,  have  been  made  in  order  to  demonstrate  in 
the  blood  the  existence  of  some  toxic  substances  which  would  exist  only 
in  Graves'  disease  and  in  no  other  condition,  and  which  might  be  regarded 
as  of  thyroid  origin.     Most  of  these  tentatives  have  been  fruitless;  not 


THYROID  OPOTHERAPY  IN  HUMAN  BEIXGS  379 

all  of  them,  however.  There  is  no  doubt  that  more  investigation  should 
be  made  in  that  direction,  and  that  with  appropriate  laboratory  methods, 
we  shall  be  able  to  isolate  many  of  these  substances  some  day. 

That  there  exists  in  the  blood  serum  of  Basedow  patients  a  substance 
which  produces  a  marked  cardiac  depression  is  certain.  Glev,  in  191 1, 
observed  that  each  time  a  serum  of  Basedow  patients  was  injected  into 
animals,  there  was  at  once  a  marked  depression  in  the  blood-pressure, 
lasting,  it  is  true,  only  for  a  short  time,  but  nevertheless  constant.  He 
showed,  too,  that  a  first  injection  of  potent  exophthalmic  serum  conferred 
a  tolerance  of  such  nature  that  subsequent  injections  of  the  same  serum 
produced  little  or  no  effect.  Blackford  and  Sanford  have  repeated  Gley's 
experiments  and  have  obtained  the  same  results.  Hence  the  conclusion 
that  the  blood  serum  of  Basedow  patients  contains  a  powerful  depressor 
substance.  This  depressor  substance  is  not  only  present  in  the  serum  of 
Basedow  patients  but  is  also  present  in  the  thyroid  gland  itself,  and  its 
depressive  power  is  in  direct  proportion  to  the  severity  of  the  disease. 
In  simple  non-toxic  goiters  this  substance  is  not  present  at  all. 

The  acetonetrile  test  of  Reid  Hunt  was  applied  to  the  serum  of 
Basedow's  disease.  It  is  known  that  with  this  method,  mice  which  have 
been  fed  with  thyroid  extract  become  at  least  ten  times  more  resistant 
to  acetonetrile  than  the  controls,  hence  the  conclusion  that  blood  serum, 
if  it  truly  contains  thyroid  products  in  excess,  should  render  mice  treated 
with  it  more  resistant  to  acetonetrile  than  normal  mice.  This  experiment 
has  been  performed  and  the  results  show  that  the  surmise  was  correct; 
indeed  the  blood  serum  injected  into  guinea-pigs  rendered  them  also 
much  more  resistant  to  acetonetrile  than  the  control.  Hence  the 
warranted  conclusion  that  blood  serum  of  Basedow  patients  contains  an 
excess  of  thyroid  products. 

Finally,  Arno  Ed.  Lampe,  experimenting  with  the  Abderhalden 
method  upon  the  blood  of  twenty-five  Basedow  patients,  came  to  the 
conclusion  that  this  blood  contains  thyroid,  thymic,  and  even  ovarian 
principles  which  do  not  exist  in  normal  individuals. 

Arguments  Derived  from  Thyroid  Opotherapy  in  Human  Beings.  But 
besides  all  these  experiments  in  animals,  there  is  a  whole  series  of  clinical 
observations  in  human  beings  which  have  the  full  value  of  experiments, 
and  which  show,  too,  that  there  is  a  direct  relation  between  the  thyroid 
and  Graves'  disease.  These  results  arc-  seen  when  a  prolonged  and 
injudicious  opotherapy  is  resorted  to. 

In  a  myxedematous  patient  who  had  ingested  ()i  grams  of  thyroid 
extract,  Beclere  noticed  a  marked  tachycardia,  tremor,  exophthalmos, 
rise  in  temperature,  increased  perspiration,  etc.  Boynet  reported  the 
case  of  a  student  who  during  a  period  of  eight  days  absorbed  6  to  8 
thyroids  of  sheep  daily,     lie  soon  developed  swelling  of  the  thyroid, 


380  ETIOLOGY  OF  GRAVES'  DISEASE 

palpitation,  tremor,  and  extremely  advanced  nervous  condition  which 
subsided  only  after  the  medication  was  stopped.  Combe  reported  the 
case  of  Gagnebin  who,  while  a  medical  student,  absorbed  daily  one  lobe 
of  sheep's  thyroid  for  a  period  of  about  two  weeks.  At  the  end  of  that 
time,  palpitation  had  become  violent,  fever  and  abundant  sweating  were 
present,  tremor  was  so  intense  that  he  could  not  rise  nor  carry  his  food 
to  his  mouth,  and  exophthalmos  had  become  very  marked;  the  experi- 
ment was  interrupted  and  the  symptoms  gradually  subsided.  Nothaft 
reports  a  very  demonstrative  case  of  a  man  who  was  in  good  health  and 
who  undertook,  on  his  own  initiative,  to  take  in  a  few  weeks  a  thousand 
thyroid  tablets  of  five  grains  each  in  order  to  reduce  his  obesity.  He 
developed  the  typical  Basedow  with  goiter,  exophthalmos,  tremor, 
sweating,  loss  of  flesh,  and  glycosuria;  the  medication  was  stopped  and 
ten  months  later  the  patient  was  normal  again.  Ferrarini  saw  the  case 
of  a  woman  who  had  taken  thyroid  as  an  antifat  cure;  she  had  taken  6 
to  8  tablets  of  thyroid  daily  for  two  months.  After  that  time  she  lost 
8  kilos,  complained  of  vertigo,  palpitations,  and  insomnia.  She  never- 
theless increased  the  quantity  of  thyroid  and  then  became  very  nervous, 
pulse  150,  diarrhea  alternating  with  constipation,  psychic  disturbances, 
hallucinations,  etc.  Kocher  saw  that  the  return  to  normal  of  the  blood 
of  a  myxedematous  patient  followed  directly  the  improvement  of  the 
patient's  condition.  When  the  patient  was  clinically  cured,  the  blood 
formula  was  normal.  If  overdoses  of  iodothyrin  were  given,  the  typical 
changes  of  the  blood  would  recur,  accompanied  this  time  by  diminished 
coagulability  of  the  blood  and  by  thyrotoxic  symptoms  such  as  tachy- 
cardia, nervousness,  tremor,  etc.  Is  it  possible  to  give  a  more  striking 
proof  that  myxedema  is  due  to  hypothyroidism,  and  Graves'  disease 
presumably  to  hyperthyroidism  ? 

A  greater  number  of  cases  could  be  cited  to  prove  the  same  conten- 
tion, and  every  surgeon  who  has  had  dealings  with  the  goiter  question, 
has,  more  than  once,  seen  patients  who  on  account  of  a  prolonged  and 
injudicious  use  of  thyroid  extract  or  iodin,  had  converted  a  simple  non- 
toxic goiter  into  a  thyrotoxic  one. 

French  undertook  to  study  the  comparative  toxicity  of  different 
tissues  in  animals  susceptible  to  thyroid  feeding,  the  object  being  to  dis- 
cover whether  the  effects  of  commercial  thyroid  extracts  when  admin- 
istered, are  specific  or  whether  similar  effects  could  be  produced  by  other 
animal  tissues  prepared  and  administered  in  the  same  way;  "Whether 
the  toxicity  is  due  to  products  of  decomposition,  or  whether  it  is  due 
simply  to  the  great  amount  of  proteid  matter  ingested  by  an  animal 
unaccustomed  to  such  a  diet."     His  conclusions  were  as  follows: 

1.  Thyroid  in  the  forms  used,  fresh,  stale,  and  desiccated,  either 
commercial  or  laboratory  prepared — contains  a  substance  that  is 
decidedly  toxic  for  some  animals. 


SURGICAL  ARGUMENT  381 

2.  The  other  animal  tissues  used,  brain,  liver,  spleen,  kidney,  and 
skeletal  muscle,  give  no  evidence  of  toxicity  when  prepared  and  fed  in 
the  same  way  in  equal  or  even  larger  quantities. 

3.  While  the  study  does  not  indicate  the  nature  of  the  toxic  substance, 
it  would  seem  to  show  conclusively  that  it  is  not  due  to  protein  in  the 
food.  This  seems  to  prove  conclusively  that  the  toxic  symptoms  found 
are  peculiar  to  the  thyroid  and  to  no  other  organs. 

Massage  of  a  non-toxic  goiter,  as  shown  by  Bneger;  radiotherapy, 
as  shown  by  Chvostek,  De  Castello  and  Schmidt;  electrical  treatment, 
as  seen  by  myself,  have  at  times,  by  stimulating  the  thyroid  gland,  pro- 
duced an  exophthalmic  goiter. 

It  cannot  be  denied  that  all  these  experiments  carry  with  them 
great  weight  which,  added  to  that  afforded  by  the  clinical  and  pathological 
data,  becomes  singularly  powerful. 

Surgical  Argument. — The  best  of  all  the  arguments  in  favor  of  the 
thyrogenetic  origin  of  Graves'  disease  is  given  by  the  results  of  surgical 
treatment.  The  number  of  cases  treated  by  this  method  now  reaches 
well  into  the  thousands;  we  have  consequently  plenty  of  material  to  draw 
our  conclusion  from.  As  seen  in  studying  the  results  of  surgical  treat- 
ment, this  latter  method  produces  50  to  85  per  cent,  of  the  cures  in  fully 
developed  cases  of  Graves'  disease  and  nearly  100  per  cent,  in  the  ones 
taken  in  their  development.  Now,  no  matter  how  little  value  one  attaches 
to  statistics,  he  cannot  but  be  impressed  by  these  figures.  We  have  seen, 
too,  that  x-rays,  radium,  injection  of  boiling  water,  etc.,  in  short,  anv 
method  intended  to  directly  attack  the  thyroid  gland  in  itself,  with  the 
purpose  of  reducing  its  size,  and  hence  of  reducing  its  function,  produces 
good  results,  although  temporary,  as  a  rule.  Why  should  it  be  so  if 
there  were  no  direct  relation  between  Graves'  disease  and  the  thyroid, 
and  why  should  it  be  so  if  the  relation  were  not  an  intimate  one  ?  This 
is  so  true  that  Riedl  has  said,  "We  would  cure  all  Basedow  cases  if  we 
could  be  allowed  to  remove  the  entire  thyroid  gland."  How  often  have 
we  surgeons  marvelled  at  the  magic  effect  of  a  simple  ligation  or  a 
thyroidectomy  upon  numbers  of  cases  of  Graves'  disease  which  had 
resisted  every  medical  treatment.  I  know  very  well  that  unfortunately 
it  is  not  so  for  every  case,  because  the  etiology  of  Graves'  disease  is  a 
most  complex  one,  as  we  shall  see  later.  But  the  fact  nevertheless  remains 
that  in  the  great  majority  of  cases  the  thyroid  must  be  the  main  guilty 
factor,  because  by  removing  a  part  of  it  we  not  only  put  a  stop  to  the 
progress  of  the  disease,  but  also  cause  its  regression.  In  the  early  stages 
the  effect  is  rapid  and  sure.  In  the  later  stages  the  result  will  depend 
upon  the  damage  clone  to  the  nervous  system,  to  the  glands  ot  internal 
secretion,  to  the  heart,  kidneys,  liver,  etc.  We  cannot  expect,  <>t  course, 
to  restore  to  normal  a  permanently   diseased   organ.     And  yet  even  in 


382  ETIOLOGY  OF  GRAVES'  DISEASE 

advanced  cases  the  surgical  treatment  is  beneficial;  rarely  does  it 
remain  without  effect. 

It  has  been  said  that  the  good  results  due  to  the  surgical  treatment 
are  of  psychic  order.  It  may  be  partially  so  in  a  few  cases  of  Graves' 
disease  complicated  with  hysteria,  but  this  is  certainly  not  the  rule. 
The  results  we  attain  are  in  direct  proportion  to  the  quantity  of  thyroid 
gland  put  out  of  function.  Why  should  it  be  so  strikingly  constant  if 
our  results  were  due  to  psychic  interference  ?  As  Crile  says  very  properly, 
"If  psychic  influences  can  cure  the  disease,  then  the  surgeon  alone  pos- 
sesses this  influence  because  all  surgical  cases  have  been  unsuccessfully 
treated  by  internists  first.  This  compliment  to  the  superior  psychic 
power  of  the  surgeon,  unhappily  we  cannot  conscientiously  accept, 
because  the  surgeon  is  unable  to  favorably  influence  his  patient  except 
at  the  time  of  his  contact  with  the  patient  on  the  operating  table,  and  at 
that  time  his  patient  is  unconscious." 

It  has  been  said,  too,  that  the  good  results  obtained  by  surgical 
treatment  were  due  to  the  forced  "rest  in  bed."  How  many  patients 
do  we  not  operate  who  have  been  taking  in  vain  the  "rest-cure"  for 
months  and  years  under  the  direction  of  possibly  the  best  internists  ? 
Why  should  we  accomplish  in  two  or  three  weeks  what  internists  failed 
to  obtain  in  months  and  years  of  the  same  "medicine."  The  argument 
is  poor  indeed. 

If  we  consider  all  the  evidence  gained  from  the  clinical  pathological, 
experimental  and  therapeutic  data  with  a  fair  and  unprejudiced  mind, 
we  are  bound  to  recognize  that  the  first  member  of  our  proposition  made 
in  the  beginning  of  the  chapter,  namely,  that  Graves'  disease  is  a  thyro- 
genic  disease  is  abundantly  demonstrated.  Although  I  am  willing  to 
admit  that  the  "irrefutable,  peremptory  argument"  is  not  yet  at  hand, 
and  that  the  one  which  might  be  considered  as  such,  as  the  experiments 
of  Klose,  should  be  confirmed,  nevertheless  the  weight  of  "circumstantial 
evidence"  is  so  strong  that  I  am  sure  that  there  is  no  jury  in  the  world 
which  would  let  a  criminal  go  free  on  the  evidence  of  charges  similar  in 
strength.  Coupled  with  the  excellent  results  which  we  obtain  with 
surgical  treatment,  this  evidence  will  still  lead  us  to  proceed  in  the  same 
line  of  treatment  until  we  get  something  better,  and  no  matter  what 
the  adversaries  of  the  thyrogenetic  theory  say,  we  will  repeat  with 
Galileo,  "E  pur  si  muove." 

B.  Nervous  Origin. — Let  us  discuss  the  second  member  of  our  proposi- 
tion, that  as  to  the  nervous  origin.  As  we  know,  there  are  some  authors 
who  consider  the  central  nervous  system  as  the  cause  of  exophthalmic 
goiter,  and  others  who  regard  that  disease  as  a  neurosis  similar  to  the  one 
seen  m  hysteria  and  epilepsy;  while  some  authors  believe  that  its  origin 
is  primarily  due  to  a  disturbance  of  the  sympathetic  system,  and  again, 


XERVOUS  ORIGIX  383 

some  others,  to  such  of  the  vagus  system.  Then,  too,  others  consider 
it  only  as  a  reflex  due  to  some  irritating  influence  taking  its  origin  in 
the  uterus,  intestines,  etc. 

That  the  glands  of  internal  secretion  in  general  are  directly  influenced 
by  the  central  nervous  system  is  abundantly  proved.  For  example, 
the  puncture  of  the  fourth  ventricle  causes  diabetes,  and  the  irritation  of 
the  subthalmic  region  causes  an  increased  function  of  the  adrenals, 
as  shown  by  Ascher.  The  section  of  the  restiform  bodies,  according 
to  Filehne  and  Warburton,  causes  hyperemia  of  the  thyroid  gland, 
exophthalmos,  tachycardia,  etc.  In  certain  psychoses,  in  neuroses,  in 
catatonia  as  shown  by  Roenfeld,  Kaufmann,  Paganim,  the  metabolism 
is  greatly  disturbed,  the  nitrogen  excretion  is  greatly  diminished,  and  the 
phosphorus  and  calcareous  elimination  greatly  increased.  The  same 
is  true  in  Graves'  disease. 

We  must  therefore  recognize  that  the  nervous  system  plays  a  very 
important  part  in  exophthalmic  goiter;  whether  this  influence  is  primary 
or  secondary  is,  however,  another  matter. 

To  be  sure,  in  Graves'  disease  the  nervous  system  is  unstable.  There 
is  a  certain  train  of  nervous  symptoms  such  as  emotionality,  irritability, 
restlessness,  instability,  which  forms  an  integral  part  of  the  clinical  syn- 
drome of  that  condition  and  which  is  just  as  typical  of  the  disease  as 
tachycardia,  tremor,  exophthalmos,  etc.  These  nervous  symptoms  are 
sometimes  the  dominant  feature  in  the  whole  syndrome.  To  consider 
them,  a  priori,  and  always  as  the  primary  cause  of  the  disease  seems  to  me, 
however,  quite  premature.  We  have  nothing  at  hand  to  substantiate 
this  conclusion;  we  have  very  much  against  it.  Moreover,  experiments 
show  that  the  nervous  symptoms  follow  administrations  of  thyroid 
extract  and  not  precede  it.  I  know  too  well,  and  I  have  admitted  it 
previously,  that  an  unstable  nervous  system  is  a  "predisposed  terrain" 
on  which  thyrotoxicosis  might  easily  graft  itself.  \\  hen  I  see  certain 
young,  nervous,  irritable,  and  unstable,  individuals,  I  cannot  help  but 
look  upon  them  as  future  candidates  for  Graves'  disease.  Possibly 
you  will  say  that  this  is  the  best  proof  that  the  disturbed  nervous  systems 
of  such  individuals  is  primarily  the  cause  of  their  thyrotoxicosis.  "  Post 
hoc,  ergo  propter  hoc."  Possibly  so;  I  am  willing  to  admit  that  it  can 
be  so  sometimes,  but  in  many  other  instances,  might  it  not  be  that  a 
number  of  these  cases  of  irritable  and  unstable  nervous  equilibrium 
are  only  latent  forms  <>t  hyperthyroidism  which  go  unrecognized,  and 
which  may  never  go  any  further  or  which  may  some  day  explode  into  a 
typical  Graves'  disease?  In  fact  I  know  that  in  some  cases  it  is  so,  as  I 
have  operated  on  some  such  cases  with  the  most  gratifying  results. 

In    studying    the    nervous    symptoms    in    connection    with    Graves 
disease  we  came  to  the  conclusion  that  the  Other  forms  of  nervous  clis- 


384  ETIOLOGY  OF  GRAVES'  DISEASE 

turbances  as  melancholia,  psychoses  are  purely  accidental.  They  must 
be  considered  as  associated  complications  grafted  upon  a  predisposed 
terrain;  heredity,  psychic  as  well  as  physical  stigmata,  are  found  in  the 
psychoses  non-complicated  with  Graves'  disease  just  as  well  as  in  thyro- 
toxicosis complicated  with  mental  disturbances  and  psychoses.  We  have 
seen,  too,  that  Graves'  disease  supervening  in  such  predisposed  terrain 
is  bound  to  favor  the  eclosion  of  psychoses,  and  vice  versa;  thyrotoxicosis 
will  evolve  more  easily  in  individuals  whose  nervous  system  is  already 
unbalanced.    There  is  no  need  to  insist  further. 

Great  stress  is  laid  by  the  partisans  of  the  nervous  theory  of  Graves' 
disease  upon  the  element  of  fear,  psychic  shock,  fright,  etc.,  in  order  to 
prove  the  nervous  origin  of  Basedow's  disease.  It  is  true  that  there  are 
cases  of  Basedow's  disease  whose  incipiency  has  been  very  sudden. 
Trousseau,  for  instance,  reports  the  case  of  a  woman  whose  father  died, 
and  who  from  sorrow  developed  in  the  space  of  a  night,  a  true  case  of 
Graves'  disease  with  exophthalmos,  vascular  goiter,  etc.  Dieulafoy 
saw  a  woman  who,  after  violent  emotion,  developed  very  rapidly  an 
exophthalmic  goiter.  In  such  cases  there  seem  to  be  no  doubt  that  the 
nervous  system  is  the  primary  cause  of  the  trouble.  These  lightning 
forms,  however,  are  rare.  They  nevertheless,  carry  great  evidential 
weight  with  them  as  they  show  that  there  exists  an  intimate  relation 
between  the  thyroid  and  the  nervous  system,  and  that  Graves'  disease 
may  take  its  origin  in  a  primarily  disturbed  nervous  system. 

There  is  another  class  of  cases,  however,  where  the  starting-point 
of  the  disease  is  referred  to  a  psychic  shock  due  to  a  runaway  horse, 
an  automobile  accident,  railroad  wreck,  etc.,  but  there  thyrotoxicosis 
has  become  noticeable  only  weeks  or  months  after  the  occurrence.  For 
these  cases  the  nervous  origin  of  Graves'  disease  is  more  doubtful,  because 
the  time  elapsed  from  the  accident  to  the  development  of  the  disease  is 
quite  long.  It  must  not  be  forgotten  that  if  one  goes  into  the  history  of 
these  cases  carefully,  one  will  usually  find  that  long  before  the  accident 
occurred  there  was  a  latent  period  during  which  a  few  Basedow  symptoms 
were  already  present.  They  may  have  been  only  barely  sketched;  that 
is  enough:  the  nervous  system  of  these  patients  had  already  lost  its 
normal  equilibrium,  hence  the  ease  with  which  the  shock  of  psychic 
order  affected  it.  Indeed,  one  cannot  but  be  impressed  by  the  fact  that 
often  the  psychic  shock  to  which  the  origin  of  the  disease  is  ascribed  is 
truly  insignificant;  at  any  rate  would  be  insufficient  to  upset  a  normal 
nervous  system.  Why  is  it  so?  Either  because  at  the  time  of  the 
accident  the  disease  was  already  in  a  period  of  incubation,  so  that  the 
psychic  shock  shaped  it  into  its  definite  form  and  intervened  as  the 
"puller  of  the  trigger,"  or  because  this  nervous  system  was  in  ordinary 
conditions  unstable  and  barely  able  to  hold  its  equilibrium,  and  only 


VEGETATIVE  XERVOUS  SYSTEM  3S5 

required  an  insignificant  cause  to  tip  it  over  the  border-line.  This  latter 
possibility  appears  that  much  the  more  plausible  since  Klose,  in  order 
to  obtain  the  best  results  in  reproducing  experimentally  the  clinical 
picture  of  Graves'  disease,  resorted  to  highly  nervous  fox  terriers.  It 
is  further  corroborated  by  the  fact  that  the  same  shock  will  affect 
one,  and  not  another.  For  instance,  did  all  the  survivors  of  the  Titanic 
disaster  develop  Graves'  disease  ?  Not  by  any  means,  vet  they  all 
underwent  the  same  ordeal. 

Aside  from  a  few  exceptions,  it  must  be  further  positively  proclaimed 
that  in  the  great  majority  of  cases  of  Graves'  disease  psychic  shock 
cannot  be  accused  of  being  the  causative  factor  simply  because  it  was 
not  present.  Surely  no  one  is  going  to  claim,  for  instance,  that  all  the 
secondary  or  Basedowified  goiters  are  of  psychic  origin,  that  a  runaway 
accident,  or  a  railroad  wreck,  is  at  the  bottom  of  all  the  primary  forms  of 
Basedow's  disease,  or  that  a  scare  by  a  burglar,  or  a  rape  by  a  negro,  is 
responsible  for  the  cases  of  Graves'  disease  following  acute  infections, 
acute  thyroiditis,  and  furthermore,  that  disappointed  love  must  be  looked 
for  in  all  the  cases  of  Graves'  disease  occurring  at  the  time  of  puberty 
and  menopause.  In  the  great  majority  of  all  these  cases  there  is  no 
apparent  cause  at  all  for  the  development  of  the  disease.  To  claim  that 
these  cases  are  primarily  of  nervous  origin  is  simply  to  make  a  statement 
founded  upon  no  proof. 

Vegetative  Nervous  System. — The  vegetative  life  is  under  the  control 
of  two  great  nervous  systems,  the  sympathetic  and  the  autonomous; 
the  latter  comprises  chiefly  the  oculomotors,  vagi,  and  the  pelvic  nerves. 
In  normal  conditions  these  two  systems  are  antagonistic;  what  one 
accelerates,  the  other  moderates,  and  vice  versa;  for  instance,  the 
cardiac  action  is  accelerated  by  the  sympathetic  and  diminished  by  the 
vagus  system;  intestinal  peristalsis  is  paralyzed  by  the  sympathetic 
and  accelerated  by  the  vagus  system.  The  welfare  of  the  organisms 
depends  upon  the  harmony  and  intelligent  working  of  the  two  systems; 
as  soon  as  one  of  them  becomes  aggressive  and  overdoes,  then  the  equilib- 
rium is  broken  and  disturbances  follow. 

The  same  system,  be  it  sympathetic  or  vagus,  contains  acceleratory 
and  moderatorv  fibers.  For  example,  besides  cardiac  acceleratory  fibers, 
the  sympathetic  contains  cardiac  moderatorv  fibers,  and  besides  modera- 
tor)' fibers,  the  vagus  contains  also  acceleratory  fibers.  It  is  true  that 
the  acceleratory  fibers  found  in  the  vagus  and  the  moderatory  fibers 
contained  in  the  sympathetic  are  far  less  numerous  than  then  antagonists, 
yet  they  exist,  and  must  come  into  play  in  some  way  or  another.  1  his 
shows  that  the  same  system  can  be  acceleratory  and  moderatorv  at  the 
same  time,  a  fact  very  important  to  remember,  as  it  shows  that  the 
duality  of  function  of  an  organ  is  possible.  This  dual  function  most 
25 


386  ETIOLOGY  OF  GRAVES'  DISEASE 

likely  occurs  through  the  influence  of  hormones  acting  electively  and 
exclusively  upon  each  set  of  fibers. 

This  notion  of  "duality  of  function"  of  the  same  organ  is  an  exceed- 
ingly important  one  to  remember.  It  must  be  safe  to  say  that  the  nervous 
system  cannot  be  the  only  one  to  have  this  peculiarity,  but  that  other 
organs  must  certainly  share  the  same  property.  This  must  be  especially 
true  for  the  organs  of  internal  secretion.  And  so  it  is.  As  shown  by 
Eliot,  small  doses  of  adrenalin  produce  a  vasodilatation  of  the  blood- 
vessels, whereas  in  higher  doses  it  produces  a  vasoconstriction.  Pituitrin 
increases  the  contractions  of  the  gravid  uterus  of  a  rabbit,  whereas 
it  paralyzes  the  non-gravid.  Iscovesco  isolated  from  the  glands  of  internal 
secretion  various  lipoids,  each  one  possessing  a  definite  property,  although 
coming  from  the  same  gland;  in  that  case  the  function  instead  of  being 
dual  ma}r  be  manifold.  This  principle  being  accepted,  at  once  the  horizon 
widens  and  facts  which  at  first  seemed  to  contradict  themselves,  as  for 
instance  the  simultaneous  presence  of  hypothyroidism  and  hyper- 
thyroidism symptoms  become  intelligible. 

Excitation  of  the  sympathetic  nerve  causes  tachycardia,  exophthalmos, 
alimentary  glycosuria,  enlargement  of  the  palpebral  fissure,  and  increased 
metabolism.  On  the  other  hand,  excitation  of  the  vagus  causes  sweating, 
vomiting,  diarrhea,  lymphocytosis.  Adrenalin  produces  the  same  effect 
as  does  the  excitation  of  the  sympathetic,  namely,  an  excitatory  action 
whenever  the  sympathetic  fibers  are  excitatory,  or  paralyzing  whenever 
they  are  inhibitory.  On  the  other  hand,  small  doses  of  pilocarpine  or 
muscarine  stimulate  the  vagus  system;  at  the  same  time  they  stimulate 
the  sympathetic  fibers  which  supply  the  sudoriparous  glands.  Atropin 
paralyzes  the  vagus  system  and  the  sympathetic  fibers  supplying  the 
sudoriparous  glands. 

Since  by  feeding  animals  or  human  beings  with  thyroid  extracts,  we 
obtain  results  which  resemble  very  much  the  ones  seen  after  the  adminis- 
tration of  pilocarpine  or  muscarine,  such  as  vomiting,  diarrhea,  lympho- 
cytosis, eosinophiha,  sweating,  respiratory  disturbances,  etc.,  it  is  logical 
to  conclude  that  there  exists  in  the  thyroid,  substances,  or  better,  hormones, 
whose  effects  are  similar  to  that  of  pilocarpine,  and  which  act  electively 
upon  the  vagus  system.  Furthermore,  since  a  number  of  other  symptoms 
seen  in  Graves'  disease  are  exactly  similar  to  the  ones  obtained  by  irrita- 
tion of  the  sympathetic,  such  as  tachycardia,  alimentary  glycosuria, 
enlargement  of  the  palpebral  fissure,  exophthalmos,  increased  metab- 
olism, etc.,  and  since  the  ingestion  of  thyroid  extract  produces  the  same 
troubles,  it  is  rational  to  conclude  that  either  the  thyroid  contains  one 
or  more  hormones  acting  electively  upon  the  sympathetic  system,  or 
that  the  thyroid  hormones  act  upon  other  organs  such  as  the  suprarenal 
bodies,  whose  adrenalin  then  influences  the  sympathetic  system. 


VEGETATIVE  XERVOUS  S  VST  EM  387 

But  there  is  something  more.  Small  doses  of  pilocarpine  which  in 
normal  individuals  will  have  little  or  no  effect,  may  produce  intense 
symptoms  in  other  individuals,  hence  the  conclusion  that  the  vagus 
system  of  the  latter  subjects  is  normally  in  a  state  of  hypertonics  because 
an  excitant,  which  normally  would  remain  without  effect  is  sufficient 
to  cause  in  them  marked  symptoms.  Hesse  and  Eppinger  say  that  these 
individuals  whose  vagus  system  is  in  a  state  of  constant  hypertonus  are 
vagotonic,  and  call  vagotrope  the  substances  which  act  upon  the  vagus 
svstem.  These  vagotonic  individuals  are  normally  sensitized  to  vago- 
tropic substances;  at  the  same  time  they  remain  more  or  less  refractory 
to  substances  which  ordinarily  act  upon  the  sympathetic  system. 

The  same  is  true  for  the  sympathetic.  Substances  which  in  normal 
individuals  will  cause  little  or  no  effect  upon  their  sympathetic  system, 
will  prove  very  active  in  certain  other  individuals.  Again,  according  to 
Hesse  and  Eppinger,  the  sympathetic  system  of  the  latter  individuals  is 
in  a  state  of  constant  hypertonus;  these  individuals  are  sympatheti- 
cotonic,  and  the  substances  which  act  upon  the  sympatheticotonic 
individuals  are  sensitized  to  sympatheticotrope  substances.  At  the  same 
time  in  such  individuals  the  vagotrope  substances  given  in  large  doses 
remain  without  effect;  they,  too,  seem  to  be  inhibited.  The  vagotonus  is 
determined  by  the  excess  secretion  of  the  vagotrope  hormones  accom- 
panied at  the  same  time  by  a  diminished  secretion  of  the  sympathetico- 
trope hormones.  The  sympatheticotonus  is  caused  by  an  excess  secretion 
of  the  sympatheticotrope  hormones  accompanied  at  the  same  time  by  a 
diminished  secretion  of  the  vagotrope  hormones. 

The  thyroid  consequently  contains  sympatheticotrope  and  vago- 
trope hormones.  In  Basedow's  disease  both  varieties  of  hormones  are 
increased  and  both  act  electively  upon  the  sympathetic  and  vagus 
systems,  hence  the  mixed  symptoms  taking  their  origin  in  the  sym- 
pathetic as  well  as  the  vagus  disturbances.  The  fact,  being  admitted  with 
Eppinger  and  Hesse,  that  there  are  patients  who  are  normally  vagotonic 
or  sympatheticotonic,  it  will  naturally  follow  that  in  such  individuals 
some  of  the  thyroid  hormones  will  center  their  effects  mostly  upon  the 
already  sensitized  system:  if  the  vagus,  for  instance,  happens  to  be  the 
one  which  is  in  constant  hypertonus,  vagal  symptoms  will  be  more 
marked  than  the  sympathetic  ones,  hence  we  will  have  marked  vomiting, 
diarrhea,  sweating,  etc.,  whereas,  on  the  other  hand,  it  the  sympathetic 
is  the  one  already  sensitized,  the  poisonous  hormones  of  the  thyroid  will 
center  their  effect  mostly  upon  that  system,  hence  the  predominance 
of  tachycardia,  exophthalmos,  glycosuria,  etc.  Purely  vagotonic  or 
m  mpatheticotonic  cases  are  rare;  as  a  rule  they  are  mixed.  Consequently 
the  degree  of  vagotonicity  or  sympatheticotonicity  ol  the  organs  will 
to  a  certain  extent  determine  the  nature  of  the  thyrotoxic  syndrome  and 


388  ETIOLOGY  OF  GRAVES'  DISEASE 

its  intensity,  hence  the  explanation  why  thyrotoxic  cases  are  not  all 
alike,  and  why  the  entire  symptom-complex  of  Graves'  disease  is  not 
always  met  in  one  case.  Thus  it  will  be  understood  that  it  is  not  neces- 
sary to  have  a  large  goiter  in  order  to  have  a  severe  Basedow,  if  one 
happens  to  be  normally  vagotonic  or  sympatheticotonic  or  both.  Thus 
it  will  be  understood  too,  that  it  is  not  necessary  that  the  whole  gland 
be  hyperplastic,  but  that  isolated  areas  of  localized  hyperplasia  will 
suffice  to  cause  the  thyrotoxic  syndrome,  because  these  areas  will  send 
what  Kocher  in  the  forethought  of  his  genius  called,  "  Basedow  impulses," 
and  which  are  nothing  else  than  lipoids  acting  electively  upon  already 
sensitized  organs.  Thus  this  will  finally,  to  a  certain  extent  at  least,  as 
other  factors  intervene,  afford  a  reasonable  explanation  for  the  fruste 
forms  of  Graves'  disease. 

Let  us  conclude:  The  nervous  system  takes  in  the  production  of 
Graves'  disease  a  very  active  and  important  part.  Although  the  nervous 
system  may  in  a  few  cases  be  primarily  affected,  in  the  remainder  of 
the  cases  it  is  only  secondarily  involved. 

C.  Polyglandular  Origin. — This  is  the  third  member  of  our  proposi- 
tion. If  one  takes  a  bird's-eye  view  of  the  symptoms  due  to  disturbances 
of  each  one  of  the  organs  of  internal  secretion  separately  and  compares 
them  with  each  other,  besides  the  typical  and  characteristic  symptoms 
due  to  the  pathology  of  the  gland  itself,  there  is  a  train  of  secondary 
symptoms  which  occurs  in  almost  every  disturbance  of  these  organs. 
Example :  Suppose  we  deprive  a  young  woman  of  her  ovaries :  besides  the 
complete  amenorrhea  and  loss  of  sexual  appetite,  we  shall  observe  hot 
flashes,  sweating,  palpitation,  moderate  tachycardia,  nausea,  glycosuria, 
vomiting,  nervousness,  cutaneous  eruptions,  depressive  states,  and 
sometimes  temporary  insanity.  And  again,  take  Addison's  disease,  for 
instance;  there,  too,  besides  profound  myasthenic  symptoms  characterized 
by  an  intense  feeling  of  excessive  fatigue,  going  sometimes  into  a  state  of 
complete  adynamy,  and  besides  melanodermy,  there  is  a  group  of  more 
general  symptoms  present,  such  as  complete  loss  of  appetite,  vomiting, 
diarrhea,  alternating  sometimes  with  constipation,  polyuria,  and  poly- 
dipsia, headache,  loss  of  sleep,  nervousness,  states  of  depression,  low 
blood-pressure,  flabby  heart,  irregularity  of  menstrual  function,  and 
sometimes  complete  amenorrhea.  And  so  on.  The  same  is  true  in  a 
general  way  for  the  pathological  conditions  of  the  other  organs  of 
internal  secretion. 

It  we  compare  these  clinical  symptoms  with  the  ones  seen  in  Graves' 
disease,  we  are  forced  to  admit  that  a  number  of  them  found  in  the  latter 
condition  seem  to  be  common  to  diseases  of  other  organs  of  internal 
secretion,  although  in  every  instance  the  organ  primarily  involved  is  an 
entirely    different   one.      This    must    mean    consequently    that    there    is 


POLYGLANDULAR  ORIGIN  389 

between  all  these  organs  a  functional  interrelation.  And  so  it  is,  as 
shown  by  the  pathology  and  by  experimentation.  No  one  organ  is  inde- 
pendent of  the  other  organs.  There  is  no  one  organ  driving  the  other 
organs  exclusively,  but  rather  do  the  organs  drive  each  other  reciprocally. 
There  is  here  no  solar  system  around  which  everything  else  gravitates. 
Our  organism  is  not  an  autocracy  but  a  democracy.  To  be  sure,  some 
organs  are  more  important  than  others,  but  they  are  nevertheless 
dependent  upon  the  less  important  and  vice  versa.  Whenever  one 
becomes  pathologically  involved,  its  derangement  repercusses  upon  the 
function  of  the  others.  There  is,  in  other  words,  a  functional  solidarity 
among  them  all.  This  solidarity  is  not  only  functional,  but  is  compen- 
sator)*, too.  For  example,  if  one  of  the  hemispheres  of  the  brain  is 
removed,  there  is  a  compensatory  hyperideation  in  the  other  hemisphere. 
When  a  large  bloodvessel  becomes  obstructed  for  some  reason  or  another, 
and  incapable  of  carrying  the  blood  through  the  normal  channel,  a  collat- 
eral circulation  takes  place  in  order  to  relieve  the  flood;  and  of  this  no 
better  example  can  be  given  than  that  of  the  caput  medusae  resulting 
from  obstruction  of  the  portal  vein.  If  one  kidney  is  removed,  the  other 
one  compensates  its  loss  by  hypertrophy  and  increased  function.  And 
so  on.  The  thyroid  does  not  make  an  exception  to  these  laws.  Let  us 
see  if  we  can  base  our  views  upon  something  tangible. 

Thyroid  and  Hypophysis. — Boise  and  Biedl  found  a  marked  hyper- 
trophy of  the  hypophysis  in  two  cases  of  myxedema  and  in  one  of  sporadic 
cretinism.  Schonemann  and  Comte  found  an  hypertrophy  of  the  hypo- 
physis whenever  the  thyroid  was  degenerated  or  atrophied.  Rogowitsch 
found  a  constant  hypertrophy  of  the  hypophysis  after  complete  thyroidec- 
tomy had  been  performed.  Guerrmi  and  Dehlle,  after  treating  various 
animals  with  thyroid  extract  found  that  there  was  more  or  less  constantly 
an  hypertrophy  of  the  hypophysis.  Hyperemia  of  the  hypophysis  has- 
been  found  in  connection  with  Graves'  disease.  It  is  logical  to  admit 
that  the  hypophysis  participates  functionally  in  the  production  of  the 
thyrotoxic  syndrome  because  vasomotor)'  disturbances,  variations  of 
temperature,  increased  sensation  of  thirst,  and  polyuria  arc  commonly 
seen  in  diseases  of  the  hypophysis.  The  disturbed  metabolism  of  fat  and 
the  cutaneous  eruptions  seen  in  Graves'  disease  are  likely  due  to  disturb- 
ances of  the  hypophysis.  Alquier  and  Hallion,  alter  feeding  rabbits 
with  hypophysis  extract,  found  vasoconstriction  of  the  thyroid  gland  and 
finally  shrinkage  of  the  whole  gland.  As  seen  by  our  pathological  and 
experimental  data,  there  is  on  the  whole  little  doubt  of  the  existence 
of  some  sort  of  specific  relation  between  the  thyroid  and  the  hypophysis. 

Thyroid  and  the  Genital  System.  That  there  is  a  relation  between 
the  thyroid  and  the  genital  apparatus,  is  shown  bv  the  fact  that  the 
great  majority  of  Basedow  patients  are  women,  and  that  the  djseast   in 


390  ETIOLOGY  OF  GRAVES'  DISEASE 

influenced  materially  by  menstruation,  pregnancy,  and  menopause. 
The  constitutional  difference  between  man  and  woman  is  due  solely 
to  the  genital  apparatus.  More  than  men,  women  are  all  their  lives 
under  the  constant  influence  of  their  genital  system.  This  influence 
begins  at  the  time  of  puberty,  keeps  up  with  each  menstruation,  and  only 
stops  at  the  menopause.  During  all  these  periods  not  only  the  nervous 
system  is  jeopardized,  but  the  entire  organism  is  in  a  state  of  constantly 
changing  equilibrium,  hence  the  tendency  for  women  to  develop  Graves' 
disease  more  frequently  than  men. 

As  we  have  seen  in  studying  the  disturbances  of  the  genital  system, 
in  Graves'  disease  menstruation  is  often  irregular,  and  not  infrequently 
totally  absent.  This  total  amenorrhea  may  remain  permanent  and  may 
then  give  rise  to  a  premature  menopause.  Hand  in  hand  with  these 
genital  disturbances  there  often  goes  hypoplasia  of  the  genital  system. 
This  atrophy  is  found,  too,  in  hypothyroidism.  When  myxedema  occurs 
in  adults  it  is  not  infrequent  to  see  a  complete  reversion  to  sexual 
infantilism  marked  by  atrophy  and  impotence.  For  instance,  Lanz 
reported  the  case  of  a  man  who  had  become  myxedematous  ten  years 
after  thyroidectomy;  the  testicles  became  markedly  atrophic.  Ceni 
noted  a  marked  diminution  in  the  production  of  eggs  in  thyroidectomized 
hens.  Parhon  and  Goldstein  consider  the  thyroid  and  ovaries  as  antago- 
nistic, whereas  Charrin  and  Jardry  claim  that  they  are  synergetic. 

Thyroid;  Pancreas;  Adrenals. — There  is  no  doubt  that  there  is  between 
the  thyroid  and  the  pancreas  an  intimate  relation.  The  disturbances 
in  the  metabolism  of  carbohydrates  so  often  seen  in  Basedow's  disease 
must  be  attributed  to  a  disturbed  function  of  the  pancreas.  The  same 
is  true  for  the  disturbed  resorption  of  fat  which  gives  rise  to  fatty  stools. 
Chvostek  was  among  the  first  in  determining  these  facts  by  showing 
that  certain  cases  of  Basedow  were  caused  by  disturbances  of  the  pan- 
creas, and  that  the  symptoms  would  retrocede  after  pancreas  opotherapy. 
Kohn  and  Peiser  confirmed  Chvostek's  conclusions,  basing  their  state- 
ment upon  postmortems  of  thyrotoxic  patients  in  which  undoubted 
pancreatic  lesions  were  found.  Eppinger,  Falta,  Rudinger,  Grey  and 
De  Sautelle  have  noted  that  glycosuria  could  be  produced  experimentally 
in  dogs  by  giving  them  large  doses  of  adrenalin;  and  that  glycosuria  does 
not  take  place  at  all  if  thyroidectomy  has  been  performed.  This  will 
explain  why  myxedematous  patients  can  stand  very  large  doses  of  sugar 
without  showing  alimentary  glycosuria.  Falta  has  reported  one  case  in 
which  after  thyroidectomy  marked  hypertrophy  of  the  islands  of 
Langerhans  was  found. 

Lately  Rudinger,  Falta,  and  Eppinger  have  shown  that  the  thyroid, 
the  pancreas,  and  the  adrenals  were  intimately  related  and  exerted  a 
reciprocal  action  one  upon  the  other  (Fig.  70).     According  to  them  the 


POLYGLANDULAR  ORIGIN  391 

pancreas  inhibits  the  thyroid  and  the  chromaffin  system,  the  adrenals 
inhibit  the  pancreas  and  stimulate  the  thyroid,  while  the  thyroid  also 
inhibits  the  pancreas  and  stimulates  the  adrenals  (Fig.  70).  Conse- 
quent!)', the  thyroid  and  the  pancreas  on  the  one  hand,  and  the  chro- 
maffin system  and  the  pancreas  on  the  other  hand,  are  antagonistic, 
whereas  the  thyroid  and  the  chromaffin  system  are  synergetic.  From 
this  it  follows  that  the  hyperfunction  of  one  will  have  as  a  consequence 
the  hyper-  or  hypofunction  of  the  others  as  the  case  may  be.  Hyper- 
thyroidism, consequently,  must  produce  an  insufficiency  of  the  pancreas 
and  a  hyperfunction  of  the  adrenals.  This  will  explain  why  in  pancreasec- 
tomized  animals  the  excitability  of  the  dilatator  muscles  of  the  iris 
is  greatly  increased,  and  this  is  most  likely  on  account  of  the  increased 
output  of  adrenalin.  The  same  is  true  for  animals  overfed  with  thyroid 
extract,  and  the  same  is  likewise  true  for  Basedow  patients,  who  often 
react  by  widening  of  the  pupils  after  the  instillation  of  a  few  drops  of 

Thyroid 


Pancreas 


Fig.  70 

adrenalin.  In  athyroidism  and  hypothyroidism,  the  function  of  the 
thyroid  being  diminished,  its  inhibiting  power  on  the  pancreas  is  ipso 
facto  diminished  also;  hence  the  increased  function  of  the  pancreas  which 
in  turn  results  only  in  an  increase  of  the  inhibitory  power  of  the  pancreas 
upon  the  thyroid,  thus  forming  a  vicious  circle  in  which  the  pancreas 
take  more  and  more  the  upper  hand.  At  the  same  time,  as  the  exciting 
power  upon  the  chromaffin  system  by  the  diminished  thyroid  is  reduced, 
too,  and  as  the  inhibitory  power  of  the  pancreas  upon  the  chromaffin 
system  is  increased,  we  must  likewise  have  a  diminution  of  adrenal 
function. 

Since  normally  the  pancreas  peptonizes  the  proteins  through  its 
trypsin,  saccharifies  the  amylaceous  substances  through  its  amylopsin, 
and  saponifies  the  fat  through  its  steapsin,  and  as  on  the  other  hand,  these 
various  functions  in  hyperthyroidism  are  inhibited,  so  we  must  expect 
to  find  that  the  metabolism  of  carbohydrates  is  greatly  diminished,  and 
we  must  consequently  expect  to  find  loss  of  peptones,  glycosuria,  and  fat 


392  ETIOLOGY  OF  GRAVES'  DISEASE 

in  the  stools.  And  so  it  happens  quite  frequently.  On  the  other  hand, 
the  opposite  must  be  true  in  hypothyroidism:  indeed,  it  is  a  known  fact 
that  in  that  condition  the  tolerance  for  carbohydrates  is  greatly  increased. 

Krauss  and  Fnedenthal  have  shown  that  normal  human  blood  serum 
has  no  effect  upon  the  frog's  eye;  if,  however,  thyroid  extract  is  injected,  a 
marked  mydriatic  power  of  the  serum  is  found.  This  reaction  is  very 
likely  due  to  an  increase  in  the  adrenalin  content  of  the  blood,  or  at  least, 
to  an  abnormal  amount  of  sympatheticotomc  substances  of  some  sort. 
Cam  confirmed  these  statements.  In  using  the  Meltzer-Ehrmann  test, 
many  authors  and  myself  often  found  an  increased  adrenalin  content  of 
the  blood  of  Basedow  patients;  in  many  instances,  however,  this  increase 
is  not  present.  Kostlivy,  treating  per  os  rabbits  with  thyroid  substances, 
noted  a  marked  increased  mydriatic  power  of  the  serum  proportionate  to 
the  dosage.  At  the  autopsy  the  adrenals  of  these  rabbits  showed  marked 
hypertrophy.     In  hypothyroidism  no  changes  in  the  adrenals  are  found. 

Thyroid  and  Thymus. — The  evidence  that  there  is  an  intimate  relation 
between  the  thyroid  and  the  thymus  in  Basedow's  disease  is  mostly 
clinical.  It  is  becoming  more  and  more  an  undoubted  fact  that  in  the 
great  majority  of  cases  of  Graves'  disease  there  is  at  the  same  time  a 
thymic  hyperplasia.  This  thymic  hyperplasia  is  mostly  constituted  by  a 
proliferation  of  the  medullary  portion  of  the  thymic  lobule  at  the  cost 
of  the  cortical  portion.  In  severe  cases  the  entire  thymus  consists  mostly 
of  the  medullary  substance.  At  the  same  time  there  is  an  intense  prolif- 
eration of  Hassal's  corpuscles  and  a  marked  increase  of  eosinophiles. 
The  entire  gland  is  soft  and  exudes  a  milky  juice.  Thymic  hyperplasia 
does  not  occur  in  conjunction  with  Basedow's  disease  only,  but  is  often 
found  in  simple  goiter.  R.  G.  Hoskms  found  that  the  offspring  of  female 
guinea-pigs  treated  with  thyroid  substances  often  had  hypertrophied 
thymuses.  This  fact  would  tend  to  indicate  that  the  thyroid  stimulates 
the  thymus.  Jeandehze,  Lucien,  and  Pansot  have  recently  shown  that 
thyroidectomy  in  young  rabbits  causes,  in  every  instance,  a  diminution 
of  the  thymus  as  compared  with  that  of  the  control  animal  of  equal 
size.  Wornes  and  Pigache  have  shown  the  same  results,  a  fact  which 
tends  to  prove  that  the  thyroid  and  thymus  are  synergetic. 

Thyroid  and  Parathyroids. — According  to  Tage  Iversen,  no  parathyroid 
lesions  are  found  in  Graves'  disease.  On  the  other  hand,  Alquier  and 
Hallion,  after  feeding  animals  with  parathyroid  extract,  observed  marked 
histological  changes  in  the  thyroid,  resembling  the  ones  seen  in  Basedow's 
disease,  whereas,  feeding  with  hypophysis  seemed  to  produce  exactly 
the  opposite  picture. 

Conclusions. — Although  it  is  still  difficult  to  gain  a  clear  insight  into 
this  complicated  mechanism  of  the  organs  of  internal  secretion,  there 
cannot  be  any  doubt  as  to  the  functional  interrelation  of  all  these  organs. 


IODIX -BASEDOW  393 

The  thyroid  forms  one  very  important  ring  of  the  polyglandular  chain. 
Its  pathology  repercusses  upon  the  other  organs  of  internal  secretion 
which  in  turn  react  upon  the  thyroid,  hence  a  vicious  circle. 

Summing  up,  we  are  forced  to  conclude  that,  although  the  thyroid 
gland  plays  the  most  important  part  in  the  production  of  Graves'  disease, 
we  must  nevertheless  concede  that  other  factors  intervene  at  the  same 
time,  such  as  the  nervous  and  the  polyglandular  systems.  Hence  my 
conclusion:     Thyrotoxicosis   is   a   thy roneuropoly glandular  disease. 

Let  us  see  now  if  we  can  gain  some  information  as  to  how  the  thyroid 
changes  take  place  and  what  the  intimate  working  of  the  process  is.  Let 
us  stud)-  first  the  iodin-Basedow  and  then  see  what  relation  exists 
between  Basedow's  disease  and  thyroiditis. 

IODIN  BASEDOW. 

The  use  of  any  form  of  iodin  preparation  may  cause  a  group  of  symp- 
toms known  as  iodism;  this  condition  is  mostly  characterized  by  sneezing, 
running  of  the  nose,  sensation  of  constriction  of  the  throat,  bronchitis, 
stomach  and  intestinal  catarrh,  conjunctivitis,  with  abundant  lachrymal 
secretion,  headaches,  and  skin  eruptions.  In  the  beginning  the  tongue, 
mouth  and  pharynx  are  dry;  later,  however,  abundant  salivation  takes 
place.  These  symptoms  are  due  to  the  fact  that  iodin  is  eliminated 
through  the  mucous  membrane  and  skin,  and  that  some  patients  are 
more  sensitive  than  others  to  its  influences,  or  that  they  may  have  some 
sort  of  idiosyncrasy  for  iodin.  This  form  of  iodism  is  benign  and  mostly 
harmless;  very  exceptionally  it  may  lead  to  acute  edema  of  the  glottis. 
Ordinarily  it  subsides  as  soon  as  the  iodin  treatment  is  discarded,  and 
no  ill  effects  are  felt  from  it  afterward.  As  seen  this  has  nothing  in 
common  with  the  clinical  picture  known  as  hyperthyroidism. 

An  entirely  different  proposition,  although  less  widely  known,  is 
that  of  a  certain  form  of  iodin  intoxication  which  occurs  once  in  a  while 
in  connection  with  iodin  treatment  of  goiter  and  which  closely  resembles 
the  clinical  syndrome  seen  in  thyrotoxicosis.  It  is  characterized  by 
nervousness,  tachycardia,  tremor,  palpitation,  insomnia,  gastro-intestinal 
disturbances,  depressive  conditions,  marked  loss  of  flesh,  and  a  profound 
asthenic  condition.  In  many  instances,  exophthalmos  occurs.  Rilhct, 
of  Geneva,  was  the  first,  in  1895,  whose  attention  was  called  to  that  form 
of  intoxication  and  regarded  it  as  a  sort  of  idiosyncrasy.  He  called  it 
constitutional  iodism.  Since  then  similar  observations  have  been  made 
frequently  and  the  condition  has  become  well-known  to  the  clinicians. 
Breuer  called  it  iodin- Basedow,  and  that  denomination  has  been  adopted 
by  everyone. 

Iodin-Basedow   occurs   with   predilection   in    people  of   middle   age, 


394  ETIOLOGY  OF  GRAVES'  DISEASE 

between  thirty  and  forty;  in  young  individuals  the  course  of  the  condi- 
tion is  much  more  severe.  Something  very  peculiar  is  the  fact  that 
some  patients  developing  lodin-Basedow  may  have  used  iodin  prepara- 
tions several  times  previously  and  during  more  or  less  long  periods 
without  ill  effects;  then  some  day,  for  no  apparent  reason,  the  use  of 
possibly  only  very  small  doses  of  iodin  has  been  enough  to  cause  the 
iodin-Basedow.  Women  are  more  often  affected  with  it  than  men. 
The  condition,  as  a  rule,  starts  two  or  three  weeks  after  beginning  the 
iodin  treatment,  grows  worse  as  long  as  the  medication  is  kept  up,  and 
usually  disappears  gradually  after  the  10dm  medication  has  been  dis- 
carded. It  takes,  as  a  rule,  several  months  before  the  patient's  condition 
becomes  normal  again,  sometimes  years.  Even  then  there  sometimes 
remains  a  tendency  to  palpitation,  nervousness,  etc.  In  other  instances, 
instead  of  regressing,  the  condition  progresses  gradually  and  develops 
into  a  severe  case  of  Graves'  disease;  a  fact  which  I  have  observed  more 
than  once. 

A  fact  worthy  of  notice  is  that  hand  in  hand  with  the  appearance  of 
the  iodin-Basedow  goes  a  reduction  in  the  size  of  the  thyroid  gland. 
Later,  however,  if  the  iodin-Basedow  should  grow  into  a  true  Basedow 
the  thyroid  gland  will  enlarge  again. 

Is  there  any  Relation  between  Iodin-Basedow  and  the  Quantity  of  Iodin 
Absorbed? — In  a  great  many  cases  the  smallest  doses  of  iodin  are  sufficient 
to  produce  iodin-Basedow;  cases  are  known  where  the  mere  use  of  tincture 
of  iodin  applied  once  or  possibly  twice  to  the  skin  or  gums  was  sufficient 
to  cause  the  condition.  On  the  other  hand,  it  is  known,  too,  that  some 
individuals  may  stand  the  most  prolonged  and  large  doses  of  iodin  without 
the  slightest  ill  effect  except  possibly  some  lodism.  We  are  consequently 
forced  to  conclude  that  the  quantity  of  10dm  is  in  itself  irrelevant. 

The  time  which  elapses  from  the  beginning  of  the  intake  of  iodin  to 
the  time  when  the  symptoms  of  iodin-Basedow  develop  is  variable; 
ordinarily  iodin-Basedow  occurs  ten  to  fifteen  days  after  the  beginning 
of  the  iodin  medication;  in  some  instances,  however,  it  may  begin  only 
weeks  after  the  iodin  medication  has  been  stopped. 

It  has  been  observed  that  m  countries  where  goiter  is  endemic,  iodin 
treatment  is  very  apt  to  cause  an  iodin-Basedow.  Fleishmann  has  shown 
that  susceptibility  to  iodin  varies  not  only  with  each  individual  but  also 
with  regions:  for  instance,  persons  living  in  Geneva,  or  Vienna  are  more 
susceptible  than  others  living  in  other  cities;  68  per  cent,  of  the  patients 
seen  in  Basel,  23  per  cent,  in  Berne,  and  3.7  per  cent,  in  Berlin  when 
treated  with  iodin  showed  symptoms  of  iodin-Basedow.  Why  such  a 
difference  ?    Nobody  knows. 

Iodin-Basedow  resembles  so  clearly  the  ordinary  Basedow  that  we 
are  forced  to  admit  that  both  conditions  are  alike,  and  are  due  to  the 


IODIN -BASEDOW  395 

same  cause,  namely,  to  hyperthyroidism.  There  is  between  them 
only  a  difference  of  degree.  The  iodin-Basedow  which  might  be  called 
alimentary  hyperthyroidism  bears  to  the  ordinary  Basedow  the  same 
relation  that  alimentary  glycosuria  does  to  diabetes.  The  first  form  is 
transitory;  the  second  is  permanent,  but  both  forms  apparently  recog- 
nize the  same  cause,  no  matter  by  what  mechanism  the)'  occur. 

There  can  be  no  doubt  that  iodin-Basedow  is  due  to  the  disturbed 
metabolism  of  iodin.  We  have  said  before  that  whenever  an  iodin- 
Basedow  begins  to  develop,  there  is  at  the  same  time  a  concomitant 
reduction  in  the  size  of  the  thyroid  gland.  It  is  true,  however,  that  after  a 
while  the  thyroid  returns  to  its  previous  size  and  often  exceeds  it.  What 
does  this  mean  ?  It  can  signify  but  one  thing,  namely,  that  the  thyroid 
gland  is  reducing  its  size  by  throwing  off  into  the  blood  circulation  a 
certain  amount  of  its  content.  What  can  this  content  be  if  it  is  not  the 
''colloid"  itself,  and  where  can  the  gland  throw  it,  if  not  into  the  general 
circulation  ?  In  other  words,  iodin  stimulates  resorption  so  that  the 
organism  finds  itself  rapidly  flooded  with  thyroid  products.  As  the  process 
goes  on,  however,  the  thyroid  increases  its  secreting  power  by  redupli- 
cation of  the  functionating  parenchyma:  hence,  again,  increase  in  volume 
of  the  thyroid.  We  know,  on  the  other  hand,  that  the  "colloid  secretion 
of  the  thyroid  gland  is  formed  mostly  by  "thyreoglobulin"  which  has  a 
great  affinity  for  iodin;  as  soon  as  it  has  fixed  the  radical  "iodin"  it 
becomes  then  "iod-thyreoglobulin."  The  higher  the  iodin  content  of 
the  iod-thyreoglobulin,  the  higher  its  activity.  These  are  the  facts. 
How  shall  we  bring  them  together  and  set  forth  a  suitable  explanation 
for  the  origin  of  iodin-Basedow? 

One  fact  seems  impossible  to  deny,  namely,  that  the  whole  problem 
seems  to  hinge  upon  a  defective  metabolism  of  iodin.  This  is  proved  by 
the  occurrence  of  iodin-Basedow  after  iodin  medication,  by  the  fact 
that  Basedow  glands  contain  a  lesser  amount  of  iodin  than  any  other 
form  of  goiter  or  normal  thyroid.  It  is  further  corroborated  by  the  fact 
that  thyroid  products  are  toxic  in  direct  proportion  to  their  iodin  content. 
That  much  is  certain. 

Another  thing,  too,  seems  to  be  more  than  probable:  it  is  the  fact 
that  anorganic  iodin  as  such  is  more  or  less  inert;  in  order  to  be  utilized 
by  the  organism,  and  in  order  to  become  useful  or  harmful  it  must  be 
combined  with  some  albuminous  substances.  In  the  thyroid  the  anor- 
ganic iodin  unites  to  thyreoglobulin  and  thus  becomes  an  organic  iodized 
preparation  which  only  then  becomes  capable  of  exerting  its  influence 
upon  the  metabolism.  This  will  explain  why  anorganic  iodin  alone  is 
inactive  in  hypo-  and  especially  in  athyroulism;  in  order  to  become 
therapeutic  iodin  must  be  combined  with  tin-  thyroid  products  whose 
activity  increases  in  direct  proportion  to  their  iodin  content.     It  would 


396  ETIOLOGY  OF  GRAVES'  DISEASE 

seem  that  in  ordinary  conditions  where  a  surplus  of  iodin  is  present  in  the 
body,  the  organism  should  not  be  worse  off  for  it,  as  the  thyroid  and  the 
other  organs  presiding  over  the  metabolism  of  10dm  ought  to  dispose  of 
it  very  quickly.  In  some  instances,  however,  for  some  reasons  still 
unknown  to  us,  matters  go  differently.  Is  it  because  of  "special  disposi- 
tion," "idiosyncrasy,"  be  it  temporary  or  permanent,  of  the  individual 
toward  iodin,  or  because  the  great  oxydating  power  of  the  iodin  directly 
activates  the  epithelial  elements  and  drives  them  to  overfunction,  or  is  it 
not  because  iodin  causes  a  toxic  thyroiditis  ?  We  know  that  in  iodin- 
Basedow  the  histological  changes  are  the  same  as  the  ones  seen  in  any 
other  form  of  toxic  or  bacterial  thyroiditis.  Hyperemia  of  the  gland 
takes  place;  cellular  hypertrophy  and  hyperplasia  occur;  the  thick 
colloid,  rich  in  iodin,  undergoes  liquefaction  and  is  quickly  absorbed 
and  thrown  into  the  circulation  under  the  form  of  an  iodized  albuminous 
substance  mostly  iod-thyreoglobulin.  Inasmuch  as  undoubtedly  the 
thyroid  has  lost  its  power  to  metabolize  iodin  in  the  right  way,  it  works 
at  top  speed  in  order  to  eliminate  it,  or  to  convert  it  into  an  ab- 
sorbable product,  hence  hyperplasia,  increased  function,  and  thyroid 
diarrhea,  as  Kocher  so  graphically  pictures  it.  Very  likely  the  iodin 
goes  through  and  irritates  the  thyroid  just  as  undigested  food  goes 
through  and  irritates  the  intestines.  On  the  other  hand,  as  shown  by 
Oswald,  the  iod-thyreoglobulin  even  in  very  small  doses  increases 
markedly,  and  for  a  long  time,  the  excitability  of  the  vegetative  nervous 
system,  be  it  sympathetic  or  vagus;  consequently  this  increased  amount 
of  iod-thyreoglobulin,  being  constantly  poured  into  the  blood  circulation, 
lowers  the  threshold  of  the  nervous  system,  thus  increasing  its  suscepti- 
bility and  excitability.  If  it  so  happens  that  the  nervous  system  has  already 
been  sensitized  to  these  iodized  thyroid  products,  at  once  the  reaction 
will  be  intense:  the  thyroid  products  will  markedly  influence  the  nervous 
system  which  in  turn  will  "fire  back"  by  influencing  the  thyroid  gland. 
Thus,  a  vicious  circle  becomes  established;  the  thyroid  drives  the  nervous 
system  and  the  nervous  system  drives  the  thyroid.  This  will  go  on  until 
one  of  the  two  gives  out,  or  until  one  of  the  two  connecting  links  is  broken, 
as  by  thyroidectomy,  for  instance. 

We  feel  consequently  warranted  in  considering  the  true  lodin-Basedow 
as  a  toxic  thyroiditis  causing  toxic  neurosis  due  to  the  influence  of  the 
iod-thyreoglobulin  upon  the  cerebrospinal  and  visceral  nervous  systems. 
The  primary  lesion,  however,  is  found  in  the  thyroid. 

THE  RELATION  BETWEEN  BASEDOW'S  DISEASE  AND  THYROIDITIS. 

The  relation  between  infectious  diseases  and  thyrotoxicosis  is  more 
than  merely  accidental.     It  is  a  relation  of  cause  to  effect.     Indeed,  a 


BASEDOW'S  DISEASE  AXD  THYROIDITIS  397 

number  of  instances  may  be  cited  to  show  that  there  is  a  direct  relation 
between  the  infectious  process  and  the  development  of  Graves'  disease. 
Almost  everv  infectious  disease,  as  typhoid,  articular  rheumatism, 
scarlet  fever,  influenza,  syphilis,  tuberculosis,  etc.,  is  known  to  have 
been  followed  some  time  after  by  the  thyrotoxic  syndrome.  Gilbert 
and  Castaigne  reported  a  case  of  a  young  girl,  aged  fifteen  years,  who 
during  the  course  of  Uphold  fever  developed  a  moderate  thyroiditis, 
and  a  month  later  showed  the  classical  symptoms  of  Graves'  disease. 
Reinhold  saw  a  patient  who  during  an  attack  of  influenza  developed 
an  acute  thyroiditis,  one  lobe  being  more  involved  than  the  other. 
Three  months  after  the  patient  developed  a  classical  Basedow's  disease. 
Curiously  enough  hypertrophy  of  the  thyroid  gland  was  most  marked 
on  the  same  side  on  which  thyroiditis  had  taken  place.  De  Quervain 
saw  a  patient  who  during  repeated  attacks  of  articular  rheumatism 
developed  a  moderate  degree  of  thyroiditis  accompanied  by  unmistak- 
able symptoms  of  Graves'  disease.  The  case  of  Breuer's  is  classical. 
His  patient  wTas  taken  suddenly  sick  with  an  acute  thyroiditis  developed 
in  the  left  lobe  of  the  thyroid.  However,  four  or  five  days  after,  every- 
thing subsided;  a  few  weeks  after  the  patient  began  to  show  symptoms 
of  exophthalmic  goiter  which  rapidly  became  so  severe  that  seven  months 
later  he  died  from  the  consequence  of  his  thyrotoxicosis.  Postmortem 
showed  in  the  left  lobe  of  the  thyroid  a  small  encapsulated  abscess  which 
proved  to  be  of  staphylococcus  origin. 

D.  D.  GletnefF  reported  9  cases  of  acute  strumitis  and  thyroiditis 
followed  by  Basedow  disease.  One  of  them  was  a  child,  aged  eleven 
years.  Another  one  was  a  young  woman,  aged  twenty-four  years,  who, 
after  typhoid  fever,  developed  a  severe  exophthalmic  goiter  which  caused 
her  death  a  few  months  after. 

I  have  seen  a  young  physician,  who  one  summer  evening  while 
in  perspiration,  sat  on  his  porch  and  got  chilled.  During  the  night 
he  complained  of  intense  pain  in  the  neck.  When  I  saw  him  the  following 
morning  he  was  in  a  state  of  complete  physical  collapse,  utterly  unable 
to  stand  or  to  walk,  had  a  marked  tremor,  palpitation,  tachycardia. 
The  whole  thyroid  was  acutely  inflamed,  the  right  lobe  being  manifestly 
larger  than  the  rest  of  the  gland.  The  gland  was  very  hard  and  exceed- 
ingly painful  to  pressure,  temperature  was  1010  F.  During  the  following 
five  or  six  days  the  condition  grew  worse,  palpitation,  tachycardia, 
tremor,  and  gastro-intestinal  disturbances  being  exceedingly  trouble- 
some. The  left  lobe  and  isthmus  reached  about  three  times,  and 
the  right  lobe,  about  four  times  their  normal  size;  the  whole  gland 
remained  exceedingly  painful  and  hard;  faint  vascular  symptoms 
developed  in  it.  Graefe,  Dallrymple  symptoms  and  a  moderate  (hunt 
of  exophthalmos  became  apparent.      I  he  patient  during  all   this  time 


398  ETIOLOGY  OF  GRAVES'  DISEASE 

remained  exceedingly  nervous  and  could  not  sleep.  After  awhile, 
however,  the  symptoms  gradually  subsided,  and  after  several  months  the 
patient  regained  his  health. 

The  author  saw  a  young  woman  who  after  a  massage  treatment  for  a 
colloid  goiter  of  the  right  lobe,  and  after  a  sore  throat,  developed  an  acute 
strumitis.  Besides  the  thyroid  symptoms  such  as  swelling,extreme  pain  on 
pressure,  hard  consistency,  and  with  a  temperature  of  102  °  F.,  she  also  had 
marked  thyrotoxic  symptoms  characterized  by  palpitation,  tachycardia, 
extreme  nervousness,  tremor,  insomnia,  unquestionable  Dallrymple 
symptom,  and  a  moderate  exophthalmos,  etc.  After  a  week  everything 
subsided,  the  thyrotoxic  symptoms  included. 

I  have  had  under  observation  a  young  nurse  who  has  always  been 
in  good  health,  although  rather  nervous  and  having  a  moderate-sized 
goiter.  While  nursing  in  the  hospital,  she  was  taken  sick  with  an  acute 
tonsillitis  which  lasted  two  weeks.  During  that  short  time  the  thyroid 
increased  materially  in  size,  and  the  thyrotoxic  symptoms  became  very 
marked.  After  tonsillitis  had  subsided  entirely  the  patient  was  a  nervous 
wreck;  pulse  was  150  to  165,  tremor  intense  and  generalized  to  the  whole 
body,  nervousness  very  marked,  exophthalmos  was  very  apparent, 
Dallrymple,  Graefe,  Kocher  symptoms  were  positive,  muscular  asthenia 
was  intense.  After  several  weeks  of  medical  treatment  the  patient 
improved  enough  so  as  to  be  able  to  go  through  operation,  which  proved 
very  successful. 

A  great  many  other  cases  could  be  cited  in  order  to  prove  this  conten- 
tion, namely,  that  there  is  a  direct  relation  between  the  infectious 
process  and  the  development  of  thyrotoxicosis.  It  shows,  furthermore, 
that  the  organ  primarily  affected  in  all  these  cases  is  the  thyroid.  This 
is  of  the  utmost  importance  so  far  as  the  etiology  is  concerned. 

In  cases  similar  to  the  ones  just  cited,  where  postmortems  and  histo- 
logical examination  of  the  gland  could  be  performed,  the  microscopic 
-hanges  found  resembled  very  much  those  seen  in  thyrotoxicosis,  namely, 
hyperemia,  cellular  hyperplasia,  thinning  of  the  colloid,  leukocyte  infil- 
tration, etc.,  the  only  difference  being  that  of  degree.  Furthermore, 
in  the  chapter  devoted  to  thyroiditis,  we  have  seen  that  chemical  poisons 
such  as  phosphorus,  nitrate  of  silver,  iodin,  turpentine,  pilocarpine,  may 
cause  a  toxic  thyroiditis  characterized  by  hyperplasia,  degeneration, 
desquamation  of  the  epithelial  elements,  thinning  or  absence  of  colloid, 
more  or  less  marked  hyperemia.  The  same  is  true  in  toxic  thyroiditis 
caused  by  bacterial  toxins.  As  we  have  seen  elsewhere,  Roger  and 
Gamier,  Crispino,  Torri,  De  Quervain,  and  others  found  that  the  intro- 
duction of  bacterial  toxins  into  the  thyroid  circulation  exerted  upon  the 
thyroid  gland  about  the  same  influence  as  the  chemical  poisons;  namely, 
hyperemia,  proliferation  and  desquamation  of  the  epithelium,  diminu- 


GRAVES'  DISEASE  IS  A   TOXIC   THYROIDITIS  399 

tion  or  absence  of  the  colloid,  etc.  The  same  pathological  findings  are 
found  to  a  certain  extent  in  thyroid  glands  during  acute  infectious  pro- 
cesses. The  lesions  may  not  be  such  as  to  be  macroscopically  detectable; 
the  microscope,  however,  shows  that  these  typical  lesions  are  present. 
For  instance,  Roger  and  Gamier,  examining  40  thyroid  glands  taken 
from  patients  who  had  died  of  scarlet  fever,  diphtheria,  acute  gastro- 
enteritis, difFuse  cerebrospinal  meningitis,  peritonitis,  rabies,  and  small- 
pox, found  in  nearly  every  case  marked  histological  changes  in  the  thyroid. 
In  some  instances  the  epithelium  had  proliferated  to  such  an  extent 
as  to  form  papillary  formations  projecting  into  the  alveolar  lumen. 
At  the  same  time  cellular  desquamation  was  present,  colloid  was  thin 
or  absent,  interstitial  connective  tissue  showed  little  or  no  pathological 
changes  except  in  the  thyroids  of  patients  who  died  from  tuberculosis; 
there  a  diffuse  sclerosis  was  found.  Cnspino,  Sarbach,  Serrafini,  \  ltry 
and  Giraud  came  to  the  same  conclusions.  De  Quervain,  investigating 
the  condition  of  the  thyroid  in  45  cases  where  the  cause  of  death  was 
tuberculosis,  cancer,  cardiac,  liver  and  kidney  diseases,  peritonitis, 
puerperal  infections,  diabetes,  scarlet  fever,  smallpox,  measles,  diph- 
theria, typhoid,  pneumonia,  found  marked  changes  in  the  epithelium 
characterized  by  a  proliferation,  desquamation,  fatty  degeneration  of 
the  desquamated  cells,  thinning,  diminution,  or  absence  of  the  colloid, 
and  hyperemia  of  the  whole  gland.  In  certain  cases  he  found  mter- 
alveolar  leukocytic  infiltration.  In  patients  wTho  died  from  cancerous 
cachexia,  diabetes,  nephritis,  Addison's  disease  and  uremia,  no  patho- 
logical changes  in  the  thyroid  were  found.  Finally,  Gregor,  in  26  thyroids 
of  children  who  died  from  scarlet  fever,  found  the  same  pathological 
changes  reported   bv   all   the  other  authors. 


GRAVES'  DISEASE  IS   A  TOXIC  THYROIDITIS. 

How  shall  we  interpret  all  these  facts?  It  we  throw  them  all 
together,  the  first  conclusion  we  come  to  is  that  the  thyroid  reacts 
in  the  same  way  to  the  most  various  and  most  diverse  processes. 
For  instance,  in  thyroiditis,  be  it  bacterial  or  toxic,  we  find  hyper- 
emia, cellular  hyperplasia,  increased  absorption  of  colloid,  leukocyte 
infiltration,  thyrotoxic  symptoms.  In  iodin-Basedow  where  10dm 
seems  to  be  the  provocative  agent,  causing  very  likely  a  toxic 
thyroiditis,  we  find,  too,  hyperemia,  cellular  hyperplasia,  diminution 
and  thinning  of  the  colloid,  leukocytic  infiltration,  thyrotoxic  symp- 
toms. In  acute  infectious  processes  of  the  organism  such  as  typhoid, 
etc.,  the  gland  shows  in  a  lesser  degree,  it  is  true,  but  nevertheless  unmis- 
takably, the  same  pathological  and  clinical  signs.     Although  the  causes 


400  ETIOLOGY  OF  GRAVES'  DISEASE 

vary,  the  results  are  the  same.  In  iodin-Basedow  as  in  toxic  and  bacterial 
thyroiditis,  as  in  the  ordinary  Basedow,  the  nature  of  the  histological 
changes  and,  to  a  certain  extent,  of  the  clinical  symptoms,  is  the  same. 
There  is  only  a  difference  of  degree.  We  are  consequently  warranted 
in  concluding  that  in  thyrotoxicosis  the  mechanism  of  the  development 
of  the  disease  is  similar  to  the  one  which  occurs  in  iodin-Basedow,  and 
in  thyroiditis,  be  it  toxic  or  bacterial.  In  the  latter  conditions  the  process 
is  acute,  whereas,  in  Basedow  it  is  chronic.  Furthermore,  as  in  iodin- 
Basedow  and  acute  thyroiditis,  the  thyroid  gland  is  involved  first  and 
the  symptoms  occur  only  after,  had  we  here  only  that  proof  in  favor 
of  our  contention,  it  would  still  be  logical  to  conclude  that  in  the  great 
majority  of  cases  of  Basedow's  disease,  the  starting-point  takes  place  in 
the  thyroid.  Hence  we  disagree  with  Mickuhcz  who  claimed  that  the 
thyroid  acted  as  a  "multiphcator;"  with  Crile,  who  thinks  that  it  plays 
the  part  of  an  "activator"  inaugurated  directly  or  indirectly  by  the 
nervous  system. 

If  we  carry  our  line  of  reasoning  a  little  further,  as  in  iodin-Basedow, 
in  bacterial,  toxic,  or  chemical  thyroiditis,  the  true  nature  of  the  process 
is  a  toxic  one,  we  shall  naturally  have  to  admit  as  a  consequence  of  it 
that  in  the  true  Basedow  disease  we  have  to  deal  with  a  similar  toxic 
process,  too.  In  the  last  analysis  the  whole  question  resolves  itself 
into  a  matter  of  a  toxico-infectious  process,  in  other  words,  Graves' 
disease  is  a  toxic  thyroiditis. 

So  understood,  this  theory  will  explain  the  pain  to  pressure  so  often 
seen  in  true  thyrotoxic  goiters;  it  will  explain  the  adhesions  so  often  found 
around  the  goiter  at  the  time  of  the  operation,  even  when  no  external 
treatment,  as  iodin  or  x-rays,  has  been  used;  it  will  explain  why  in  exoph- 
thalmic goiter  the  cervical  lymph  nodes  are  hyperplastic,  why  there  is  a 
leukocytic  infiltration  throughout  the  thyroid  parenchyma;  and  it  will 
explain,  partly  at  least,  the  slight  rise  in  temperature  sometimes  seen  in 
Graves'  disease.  It  is  not  necessary  to  look  for  a  specific  thyrotoxic 
microbe  in  order  to  explain  all  these  clinical  findings;  they  may  be 
caused  by  all  the  microbes;  their  toxins;  the  products  of  auto-intoxi- 
cation; or  any  toxic  chemical  agent.  Under  the  spur  of  their  irritation  the 
thyroid  works  at  top  speed;  in  order  to  increase  its  efficiency  and  in  order 
to  suffice  for  its  tasks,  be  it  to  neutralize  or  to  eliminate  these  poisons, 
or  whatever  it  may  be,  it  increases  its  blood  supply;  it  undergoes 
hyperplasia. 

This  theory  consequently  leads  us  to  consider  the  histological  changes 
seen  in  the  thyrotoxic  thyroid  as  the  result  of  hyperj 'unction.  Hence  the 
theory  of  hyperthyroidism.  Everything  tends  to  prove  it,  especially  the 
increased  blood  supply.  Furthermore,  Askanazy,  Muller,  and  Farmer 
found  that  the  lymphatic  veins  and  connective  tissue  in  Basedow's  disease 


GRAVES'  DISEASE  IS  A   TOXIC  THYROIDITIS  401 

were  filled  with  colloid,  whence  they  concluded   that  this  disease  was 
caused  by  an  exaggerated  amount  of  colloid  reaching  the  blood. 

As  a  result  of  the  increased  function  of  the  thyroid  there  is  constantly 
in  the  blood  an  increased  amount  of  iod-thy  reoglobulin  which,  as  we  know, 
acts  electively  upon  the  central  and  vegetative  nervous  systems.  Thus  a 
constant  and  abnormal  stimulation  is  being  kept  upon  the  thyroid  bv 
the  nervous  system  which  in  turn  stimulates  the  thyroid.  Hence  the 
establishment  of  a  vicious  circle:  as  we  have  said  before,  the  thyroid 
drives  the  nervous  system  and  the  nervous  system  drives  the  thyroid. 

This  increased,  and  possibly  modified,  thyroid  secretion  through 
its  lipoids  acts  electively  upon  predisposed  organs  already  sensitized 
by  sympatheticotrope,  vagotrope,  cardiotrope,  ovariotrope,  etc.,  sub- 
stances. Sensitization  may  not  necessarily  have  been  done  previously 
by  the  thyroid:  the  polyglandular,  the  nervous  system,  etc.,  may  have 
done  it. 

This  theory  seems  to  me  to  answer  most  satisfactorily  many  ques- 
tions. Thus,  the  protean  origin  of  Graves'  disease  is  no  more  a  puzzle; 
the  remote  causes  of  it  are  indeed  numerous  and  diverse,  as  infectious 
diseases,  disturbed  polyglandular  function,  chemical  agents,  etc.,  but 
the  immediate  cause  is  always  the  same:  the  hyperf  unction  of  the  thyroid. 
Thus,  we  shall  understand  better  why  Graves'  disease  is  more  prevalent 
at  the  time  of  puberty  and  menopause.  Indeed,  besides  the  disturbed 
nervous  equilibrium,  and  possibly  just  because  of  it,  besides  the  part 
which  the  organs  of  internal  secretion  play,  toxic  products  due  to  the 
disturbed  metabolism  circulate  in  the  blood  and  become  injurious  to 
the  thyroid,  hence  toxic  thyroiditis  and  hyperfunction.  Even  in 
cases  where  the  primary  lesion  lies  in  the  nervous  system,  as  in  cases  of 
shock,  fright,  etc.,  the  theory  still  holds  good.  Indeed,  in  such  cases 
it  is  reasonable  to  admit  that  besides  the  direct  influence  from  the  nervous 
system  upon  the  thyroid,  products  of  refuse  due  to  a  suddenly  increased 
and  disturbed  metabolism  as  shown  by  sweating,  diarrhea,  vomiting, 
disturbed  renal  function,  etc.,  which  accompany  shock  are  driven  into 
the  circulation  and  may  prove  injurious  to  the  thyroid  and  incite  it  to 
overfunction.  At  least  these  injurious  stimuli  may  be  sufficient  to  start 
a  vicious  circle  between  the  thyroid  and  the  nervous  system;  when  once 
started  there  is  no  reason  for  stopping.  Both  links,  however,  namely, 
the  thyroid  and  the  nervous  system,  are  necessary  for  the  production 
of  the  disease:  let  us  not  forget  that  the  section  of  the  restiform  bodies 
causes  exophthalmic  goiter  as  long  as  the  thyroid  is  present;  it  it  has 
been  removed  previously,  the  syndrome  does  not  rake  place. 

Dysthyroidism.      There  is  a  great  deal  of  evidence  showing  thai    the 
secretion  of  the  thyroid  is  not  affected  quantitatively  and  qualitatively: 
in  other  words,  besides  hyperthyroidism  we  have  dysthyroidism.     I  lus  con- 
26 


402  ETIOLOGY  OF  GRAVES'  DISEASE 

elusion  is  based  upon  Mannesco's  experiment.  He  demonstrated  that 
the  antigen  from  a  Basedow  struma,  when  mixed  with  serum  taken  from 
thyrotoxic  patients,  prevents  hemolysis  on  account  of  the  formation 
of  antibodies.  If,  however,  the  antigen  has  been  taken  from  a  normal 
thyroid  gland  then  hemolysis  takes  place:  hence  the  conclusion  that 
the  colloidal  nature  of  the  thyroid  secretion  is  changed  qualitatively. 
Klose  is  an  enthusiastic  believer  in  the  dysthyroidism  theory.  According 
to  him,  in  ordinary  conditions  the  iodin  is  fixed  by  the  thyroid  to  some 
albuminous  substance  in  order  to  form  the  thyreoglobulin.  In  patho- 
logical conditions,  however,  the  metabolism  of  iodin  does  not  take 
place  properly.  Klose  admits  then  the  existence  of  a  hypothetical 
substance  which  he  calls,  "  Basedow-iodin,"  very  toxic,  closely  resem- 
bling the  anorganic  iodin,  and  exerting  vagotrope,  sympatheticotrope, 
cardiotrope,  ovariotrope,  influences,  thus  determining  the  thyrotoxic 
syndrome. 

That  theory  would,  of  course,  help  us  to  understand  why  it  is  not 
necessary  to  have  a  great  deal  of  hypersecretion  of  the  thyroid  if  that 
secretion  is  vitiated.  That  would  explain  the  cases  where  little  or  no 
histological  thyroid  changes  are  present,  as  the  latter  are  mostly  evidenc- 
ing hyperfunction.  Of  course,  what  part  the  hyperthyroidism  and  the 
dysthyroidism  play  in  the  production  of  the  thyrotoxic  syndrome  is  an 
open  question. 

It  is  self-evident  that  the  theory  of  dysthyroidism,  as  well  as  the 
one  of  hyperthyroidism,  although  to  a  lesser  extent,  still  lacks  the  "irref- 
utable argument."  They  both,  however,  answer  the  facts  very  well. 
The  atomical  theory  is  still  to  be  demonstrated,  yet  chemistry  fares  very 
well  seemingly  under  its  flag.  Needless  to  say  that  in  the  meantime 
let  us  hope  that  the  future  will  bring  forth  the  solution  of  the 
problem. 

Part  of  the  Thyrotoxic  Symptoms  May  be  of  Anaphylactic  Origin.  — 
It  is  more  than  probable  that  part  of  the  thyrotoxic  symptoms  observed 
are  phenomena  of  "anaphylaxis"  due  to  the  absorption  into  the  circu- 
lation of  abnormal  albuminous  thyroid  products.  The  intense  itching 
of  the  skin  without  eruptions  resembles  closely  the  itching  observed 
in  anaphylaxis.  Indeed,  the  thyrotoxic  thyroid  albuminous  substances 
may  very  well  be  enough  modified  so  as  to  act  as  a  foreign  albumin,  thus 
"anaphylactizing"  the  organism  and  producing  toxins  centering  their 
effects  upon  the  nervous  system.  This  view  is  based  upon  Schittenhelm's 
researches  which  show  that  the  substances  resulting  from  the  splitting 
of  albumins  into  secondary  products  produce  an  intoxication  similar 
to  the  one  obtained  with  peptones  and  characterized  by  fall  of  blood- 
pressure,  on  account  of  peripheral  dilatation,  leukopenia,  acceleration 
of  the  lymphatic  current,  increased  glandular  secretion,  etc.     In  short> 


GRAVES'  DISEASE  LS  A    TOXIC  THYROIDITIS  403 

according  to  Biedl  and  Krauss,  this  toxic  syndrome  resembles  closelv 
the  one  of  anaphylaxis  and  of  Basedow's  disease.  These  views  are  further 
strengthened  by  J.  W.  Jobling  and  \V.  Petersen  who  showed  that  iodin 
incubated  with  blood  serum  lowers  markedly  its  antiferment  property; 
the  serum  of  these  patients  treated  with  iodin  becomes  toxic  because  of 
autolysis  of  the  glandular  components;  a  similar  process  (absorption  of 
the  antiferment  by  agar,  kaolin,  bacteria,  etc.)  being  the  basis  of  the 
toxicity  of  the  so-called  anaphylatoxin. 

Why  is  it  that  Some  People  Have  Exophthalmic  Goiter  and  Others  Do 
Not? — Why  is  it  that  some  people  will  stand  large  amounts  of  iodin  while 
others  cannot  ?  Why  is  it  that  acute  infectious  processes  will  cause  the 
thyrotoxic  syndrome  in  some  patients  and  not  in  others  ?  Why  is  that 
a  shock,  a  fright  which  will  not  feaze  this  one,  will  cause  Graves'  disease 
in  that  one:  In  answer  to  these  questions,  I  will  sav:  Why  is  it  that 
between  two  men  falling  into  a  river,  one  will  get  pneumonia  and  the  other 
articular  rheumatism  ?  Why  is  it  that  the  liver,  and  the  pancreas  of 
certain  individuals  are  able  to  take  care  of  enormous  quantities  of  carbo- 
hydrates without  giving  rise  to  glycosuria,  whereas  in  others  they  are 
unable  to  do  so?  Why  is  it  that  mercury  will  cause  an  acute  nephritis 
in  some  individuals  and  an  acute  enteritis  in  others,  and  no  symptoms 
in  a  great  number  of  others?  Most  likely  because  the  injury  settles 
in  the  locus  minoris  resistentice.  The  same  is  true  for  the  thyroid.  There 
must  be  conditions  unknown  to  us,  but  nevertheless  existing,  which  must 
render  certain  thyroids  more  susceptible  to  injurious  stimuli  than  others, 
just  as  certain  special  conditions  must  intervene  to  inhibit  the  hepatic 
and  pancreatic  function  in  the  metabolism  of  carbohydrates,  or  to  render 
certain  kidneys  and  intestines  susceptible  to  mercury,  just  as  certain 
requirements  have  to  be  met  to  allow  the  tubercle  bacilli  to  produce 
tuberculosis.  Congenital  weakness,  heredity,  abnormal  disposition, 
abnormal  susceptibility,  disturbed  nervous  equilibrium,  unsettled  poly- 
glandular system,  all  play  their  contributing  part.  When  the  truth 
is  known,  then  very  likely  some  reduced  factor  of  safety,  some  chemico- 
biological  disturbances  or  congenital  predisposition,  will  appear  as  the 
cause  or  the  determining  causes.  As  we  have  already  said,  "Nature 
does  not  know  a  cause  but  causes." 

Summary  of  Conclusions  Concerning  the  Etiology  of  Graves'  Disease. — 
Graves'  disease  is  a  thyro-neuro-polyglandular  disease.  The  thyroid 
is  almost  always  primarily  affected;  however,  very  much  less  frequently 
the  nervous  system  can  be  the  primary  cause,  too.  There  exists  between 
them  a  mutual  interaction;  the  thyroid  drives  the  nervous  system  and 
the  nervous  system  drives  the  thyroid:  this  constitutes  ;i  vicious  circle 
which  can  be  broken  by  medical  or  surgical  treatment.  From  a  patho- 
logical and  cluneal  stand-point,  Graves'  disease  resembles  in  every  respect 


404  ETIOLOGY  OF  GRAVES1  DISEASE 

what  we  see  in  acute  thyroiditis,  be  it  toxic  or  bacterial,  and  what  we 
see  in  Iodin-Basedow  which  is,  too,  a  toxic  thyroiditis.  Hence  we  feel 
warranted  in  concluding  that  Graves'  disease  is  a  form  of  toxic  thyroiditis. 
It  is  caused  by  any  infectious  disease,  by  any  toxic  condition  arising 
from  a  disturbed  polyglandular  function,  by  a  disturbed  nervous  equilib- 
rium, by  a  disturbed  metabolism,  etc.  Under  such  conditions  the  thyroid 
secretion  is  quantitatively  and  qualitatively  affected,  and  becomes  the 
cause  of  the  pathological  syndrome.  The  symptoms  observed  in  Graves' 
disease  are  due  to  hyperthyroidism,  dysthyroidism,  disturbances  of  the 
nervous  and  polyglandular  systems,  and  probably  some  are  due  to 
anaphylaxis. 


CHAPTER   XXXVIII. 
THE  TREATMENT  OF  GRAVES'   DISEASE. 

We  have  now  reached  the  crucial  part  of  our  work.  The  most 
elaborate  researches,  the  most  beautiful  theories,  the  greatest  effort 
and  expenditure  of  energy  will  fall  short  if  they  do  not  directly  or  indiretly 
resolve  themselves  into  some  advancement  of  the  therapeutic  end, 
the  final  test  of  every  scientific  effort.  From  the  conception  one  makes  of 
the  nature  and  etiology  of  this  disease  will  derive  the  line  of  treatment. 
Internists  who  regard  Graves'  disease  as  a  neurosis  or  as  a  disturbance  of 
central  origin,  or  as  a  peculiar  and  enigmatic  trouble  of  some  sort,  no 
matter  where  it  has  its  seat,  provided  it  is  not  in  the  thyroid  gland,  still 
work  in  the  dark,  hence  the  great,  motley  mixture  of  what  is  called 
''medical  treatment."  Surgeons,  on  the  other  hand,  who  consider  the 
thyroid  as  the  "guilty  factor,"  will  experience  no  hesitancy;  their  road 
is  open;  "Heraus  mit  dem,"  Out  with  it!  A  radical  and  not  the  ideal 
means  most  assuredly,  but  the  best  we  have  at  hand  so  far,  and  the  most 
fertile  in  results.  We  all  admit  that  it  would,  of  course,  be  more  elegant, 
more  artistic,  to  be  able  to  resort  to  some  "specific  agent"  which,  injected 
subcutaneously,  intravenously,  or  taken  by  mouth,  would  bring  about  a 
sure  cure.  It  would  be  an  art  of  the  highest  type  to  be  able  to  say  to  the 
patient  as  Christ  said  to  the  lame  man,  "Arise,  take  up  thy  bed,  and 
walk."  Unfortunately,  we  are  only  men  and  not  gods,  we  think  and 
act  according  to  our  own  little  intelligence  and  limitations.  As  yet  the 
truly  "specific  agent"  has  not  been  found.  That  it  will  some  day  there 
is  no  doubt  in  my  mind.  To  find  it  will  be  the  glorious  task  of  biological 
chemistry. 

Quite  a  marked  step  forward  in  this  direction  has  been  taken  just 
recently.  By  delicate,  chemical  manipulations,  Iscovesco  was  able  to 
isolate  from  the  various  organs  of  internal  secretion,  lipoids,  main  of  them 
possessing  decided  physiological  properties.  Lipoids  are  contained  in  all 
the  organs  of  the  body.  Some  of  them  have  an  antagonistic,  others  a 
synergetic  action.  A  given  organ  contains  numerous  lipoids.  In  the 
thyroid,  for  instance,  there  are  several  lipoids,  each  one  possessing  seem- 
ingly entirely  different  properties.  One  of  the  lipoids  injected  into  voimg 
animals  produces  myxedematous  s\  mptoms;  another  produces  thyro- 
toxic symptoms,  another  causes  a  congestion  and  hypertrophy  of  the  gland 
itself.     I  lu-  ovary  contains  a  lipoid  influencing  the  ovary  itself,  another 


406  TREATMENT  OF  GRAVES'  DISEASE 

influencing  the  uterus  and  its  appendages,  and  another  influencing  the 
thyroid.  The  lipoids  which  influence  other  organs  are  called  hetero- 
stimulants;  the  lipoids  which  influence  organs  from  which  they  are  derived 
are  called  homo  stimulants  or  self -activating.  These  facts,  if  confirmed, 
will  not  only  solve  many  obscure  problems,  but  will  also  widen  consider- 
ably our  field  of  therapeutic  action.  The  isolation  of  these  different 
substances  and  their  appropriate  use  will  be  of  tremendous  value  to  the 
future  physician.  For  the  time  being,  however,  we  must  content  our- 
selves with  what  we  have  at  hand,  "medical"  and  "surgical,"  and  try 
to  make  the  best  of  it. 

If  the  shades  of  Flajani,  Graves  or  Basedow  could  come  back  into  the 
world,  they  would  certainly  be  greatly  shocked  to  see  that  the  disease 
which  bears  their  names  has  slipped  out  of  the  bosom  of  internal  medicine 
into  that  of  surgery.  Very  likely  they  would  turn  and  with  inquisitive 
and  reproaching  tone  interview  the  internist,  and  as  in  the  "Parable  of 
the  Talents,"  they  would  say,  "What  have  you  done  with  our  legacy?" 

It  is  certainly  not  through  mere  fancy  that  the  surgeon  has  become 
entranced  with  the  thyroid  question  in  Graves'  disease.  For  long  years 
it  looked  as  if  Basedow's  disease  would  remain  forever  a  medical  disease. 
So  long  as  the  nervous  symptoms,  tachycardia,  and  exophthalmos  were 
given  the  most  prominence  in  the  clinical  syndrome,  and  so  long  as  the 
goiter  was  considered  only  as  a  secondary  and  unimportant  factor,  the 
disease  seemed  to  remain  forever  the  appanage  of  the  internist,  and  "a 
noli  me  tangere"  for  the  surgeon.  As  years  went  by,  however,  with  no 
progress  made  in  curbing  the  disease,  and  with  no  new  conceptions  of  its 
etiology,  the  disease  was  languishing  in  the  painful  marasmus  of  the 
"rest  cure;"  furthermore,  although  internal  medicine  had  seemingly 
disinterested  itself  in  this  question,  two  great  men,  internists  themselves, 
Gauthier  de  Charolles  and  Moebius,  came  along  and  with  a  new  theory 
gave  a  powerful  impetus  to  the  question. 

It  is  true  that  previous  to  them  a  few  operations  had  been  performed 
for  exophthalmic  goiter  by  Kocher  and  others.  These  operations  were 
intended,  however,  to  remove  Basedowified  goiters  causing  mechanical 
symptoms.  Great  had  been  the  surprise  of  everyone  to  see  that  at  the 
same  time  the  functional  disturbances  were  relieved  also.  Hence  suspic- 
ion became  aroused,  new  but  still  undecided  etiological  conceptions, 
which,  as  just  said,  were  soon  shaped  into  a  definite  form  by  Gauthier 
and  Moebius.  In  their  judgment  the  disease  no  longer  took  its  origin  in 
some  nervous,  circulatory,  or  other  problematic  disturbances.  It  was 
no  longer  a  neurosis.  In  their  judgment  the  goiter,  which  for  so  long 
had  been  considered  as  unimportant,  was  now  the  responsible  factor;  in 
fact,  it  was  the  primary  cause  of  all  the  trouble.  That  day  Graves' 
disease  became  at  once  a  surgical  disease;  from  the  sanitaria  and  rest-cure 


T  RE  ATM  EXT  OF  GRAVES'  DISEASE  407 

places  it  jumped  into  the  operating  rooms.  From  that  time  on  it 
ceased  to  live  in  the  marasmus  in  which  it  had  been  before.  It  became 
a  burning  question  taken  up  at  once  all  over  the  world.  Since  surgerv 
has  adopted  as  one  of  its  own,  this  abandoned  child  of  internal  medicine 
it  is  only  just  to  say  that  so  far  as  pathology  and  treatment  are  con- 
cerned, great  progress  has  been  made.  It  is  to  surgery  that  we  owe  most 
of  what  we  know  today  of  Graves'  disease,  just  as  it  is  to  surgery  that  we 
owe  most  of  what  we  know  of  appendicitis,  gastric  and  duodenal  ulcer, 
gall-bladder  diseases,  etc. 

Is  There  Truly  a  Medical  Treatment  for  Graves'  Disease? — If  by  that 
we  mean  a  well-defined,  classical,  efficient,  specific,  therapeutic  line 
of  conduct  to  be  followed  in  such  cases,  then  there  is  none.  Indeed, 
there  can  be  no  doubt  of  that.  If,  on  the  other  hand,  by  "medical 
treatment,"  we  mean  anything  which  is  not  surgical,  we  must  concede 
that  there  is  such  a  thing.  With  this  form  of  treatment  everyone  feels 
at  liberty  to  "experiment"  with  whatever  he  sees  fit,  hence  the  multi- 
tude of  medical  means  employed,  as  for  instance  10dm,  arsenic,  iodides 
of  all  kinds,  bromides,  digitalis,  belladonna,  atropin,  ergotin,  ether, 
veratrum,  strophanthus,  quinine,  nux  vomica,  phosphate  of  soda,  con- 
vallaria  majalis,  etc.;  faradization,  galvanization,  currents  of  high 
frequency,  hydrotherapy  of  all  sorts;  sojourn  at  the  sea,  or  in  high 
altitudes;  gymnastics  with  Zander's  apparatus;  mountain  climbing,  etc.; 
all  imaginable  diets,  etc.,  some  authors  advising  forced  feeding,  others, 
the  hunger  cure;  some  advising  forced  drinking,  others  the  thirst  cure; 
as  mineral  waters  of  all  sorts,  and  kephir,  milk,  zoulac;  as  serum,  blood 
or  milk  of  thyroidectomized  animals,  thyrotoxic  serums;  as  finally, 
extracts  of  the  glands  of  internal  secretion,  as  adrenals,  pancreas, 
hypophysis,  ovarian  extracts,  thymus,  testicles,  etc. 

Everyone  will  admit  that  this  medical  therapeutic  gamut  is  most 
variant,  and  everyone  according  to  his  taste  can  make  his  choice.  Bur 
please  do  not  think  for  one  moment  that  I  am  trying  to  ridicule  the 
medical  treatment.  I  know  too  well  that  each  one  of  these  means 
employed  has  to  its  credit  some  improvements  and  some  cures,  and  as 
everyone  knows,  too,  that  some  patients  get  well  without  any  treatment, 
and  as  was  said  by  Mayo,  some  get  well  in  spite  of  any  treat- 
ment. Too  often  we  hear  adversaries  of  surgical  treatment  boast  that 
they  have  cured  thyrotoxic  patients  with  the  rest  cure,  with  milk  diet, 
with  Forcheimer  treatment,  and  what  not.  We  all  can  pick  out  of  our 
series,  medical  as  well  as  surgical,  some  brilliant  results  m  order  to 
support  our  contention.  That  is  not  the  point.  We  know  thai  this  is 
true.  Hut  the  pomt  is:  Of  the  total  number  of  Basedow  patients  treated 
medically  or  surgically,  what  number  improve  or  gel  well,  and  what  is 
the  death-rate:     lh;it  can  be  best  answered  by  statistics.     Vs  Riedl  has 


408  TREATMENT  OF  GRAVES'  DISEASE 

said,  "  Medicine,  like  theology,  has  its  dogmata."  When  once  established, 
it  is  difficult  to  eradicate  them  even  when  wrong.  The  danger  of  surgical 
treatment  in  Basedow's  disease  is  one  of  these  dogmata;  its  inefficacy 
is  another.     Let  us  see  what  we  can  gather  from  statistics. 

Results  of  Medical  Treatment. — Williams,  out  of  1569  surgical  cases 
showed  a  mortality  of  4  per  cent.,  a  cure  of  72  per  cent.,  while  300  medical 
cases  treated  with  the  antiserum  gave  20  per  cent,  cure,  60  per  cent, 
improvement,  10  per  cent,  no  effect,  and  10  per  cent,  death.  Baruch, 
comparing  the  results  obtained  by  operation  and  medical  treatment, 
found  for  the  cases  treated  medically:  o  per  cent,  of  cure,  5.2  per  cent, 
were  able  to  resume  their  full  work,  26.3  per  cent,  were  only  partially 
able  to  resume  their  work,  68  per  cent,  were  unable  to  work  at  all, 
whereas  the  surgical  treatment  allowed  17.9  per  cent,  to  resume  their 
full  work,  51  per  cent,  to  resume  their  partial  work.  He  furthermore 
found  that  with  medical  treatment  cardiac  hypertrophy  never  diminished, 
whereas  it  disappeared  in  70  per  cent,  of  the  operated  cases.  In  non- 
operated  cases  he  found  further,  that  exophthalmos  remained  unaffected 
in  7.6  per  cent.,  was  improved  in  69.2  per  cent.,  and  got  worse  in  23  per 
cent.,  while  in  cases  treated  surgically,  exophthalmos  disappeared  in 
39.6  per  cent.,  was  improved  in  54.5  per  cent.,  and  remained  unaffected 
in  only  3.2  per  cent.  He  reported,  too,  that  tremor  disappeared  in  JJ 
per  cent,  of  the  operated  cases  and  never  in  the  ones  treated  medically. 
White  found  that  in  108  cases  treated  medically  by  him,  21  died,  61  were 
cured,  21  improved,  and  5  remained  unaffected.  The  mortality  with 
medical  treatment  is  high;  10  per  cent,  for  Cheadle  and  Thompson,  12 
per  cent,  for  Von  Graefe,  Von  Dusch  and  Buschan.  These  figures  are 
based  upon  900  cases.  Charcot,  Williamson,  and  Stern's  death-rate  is 
25  per  cent.  Ord  and  Mackenzie,  out  of  55  cases,  obtained  10  complete 
cures,  24  improvements,  4  negative  results,  and  14  deaths.     Murray  had 

7  deaths  out  of  40  cases.  Vetlesen,  out  of  34  cases,  had  7  cures,  20 
improvements,  and  7  deaths.  Frankl-Hochwart  out  of  60  cases  found 
25  fruste  forms  which  remained  unaffected  by  treatment;  out  of  the  other 
35  cases  of  true  Basedow,  9  cures,  11  negatives,  and  15  deaths.  Lichty 
had  3  deaths  out  of  74  cases.  Sainton  was  able  to  collect  219  cases 
treated  by  serotherapy;  10  per  cent,  were  cured,  80  per  cent,  improved, 

8  per  cent,  were  failures,  and  2  per  cent,  exacerbations.  Rogers  and 
Beebe,  in  1909,  out  of  480  cases  gave  15  per  cent,  of  cure  objectively, 
10  per  cent,  cured  subjectively,  15  per  cent,  ameliorated,  and  17  per  cent, 
failures.  In  191 5  Beebe,  without  furnishing  any  statistics,  estimated 
roughly  that  he  had  treated  3000  patients  with  antiserum  with  50  per 
cent,  cure,  30  per  cent,  improvement,  and  20  per  cent,  failure.  We  must 
not  forget,  however,  that  this  author  in  a  general  way  seems  to  be  very 
sanguine  in  his  conclusions,  as  shown  by  his  recent  "cancer  cure."     In 


RESULTS  OF  MEDICAL   TREATMENT  40!) 

1910  Kocher  reported  1000  cases  treated  surgically  and  100  cases 
treated  medicallv.  The  mortality  of  the  operated  thyrotoxic  cases 
amounted  to  4.83  per  cent.,  while  the  cures  gave  80  per  cent.  From 
the  100  cases  treated  medically,  22  had  to  be  operated  because  of  the 
failure  of  the  medical  treatment  to  bring  about  a  cure,  or  at  least,  encour- 
aging improvement.  From  the  remaining  cases,  18  per  cent,  were  cured, 
27  per  cent,  improved,  33  per  cent,  remained  unaffected,  and  22  per 
cent.  died.  Syllaba  reports  51  cases  of  Graves'  disease  treated  medically; 
9  died,  4  were  failures,  27  ameliorated,  improved,  or  cured.  The  balance 
of  the  other  cases  is  not  given.  W.  H.  Becker  went  over  all  the  cases 
admitted  into  the  clinic  of  Prof.  Dr.  Voit  in  Giessen  from  1890  to  1912. 
During  that  period  of  time  40,941  patients  were  admitted.  Among 
them  were  70  cases  of  Basedow's  disease.  As  some  of  these  patients 
were  readmitted  at  various  intervals  the  true  total  number  of  patients 
amounted  to  61.  Out  of  these  61  cases  the  records  of  the  clinic  show 
that  only  1  patient  was  discharged  cured.  From  the  remaining  60 
cases,  36  were  discharged  as  improved  (60  per  cent.),  21  were  unimproved 
(35  per  cent.),  1  case  was  sent  over  to  the  surgical  clinic,  and  operated, 
then  returned  to  the  medical  clinic  for  further  treatment  with  galvaniza- 
tion of  the  sympathetic  and  thymic  opotherapy,  and  only  then  dismissed 
as  improved.  From  the  2  remaining  cases  nothing  could  be  ascer- 
tained, as  no  history  was  to  be  found.  The  treatment  used  from  1890  to 
1903  was  a  purely  symptomatic  one:  arsenic,  bromides,  rest  in  bed, 
ice-cap  for  the  heart,  while  occasionally  iron  and  baldnan,  and 
galvanization  of  the  sympathetic  were  employed.  In  1903  for  the 
hist  time  the  antithyroidine  of  Moebius  was  used  five  times  with  4 
improvements  and  1  negative  result.  Rhodagen  was  used  twice  with  1 
improvement  and  in  the  other  case  with  only  a  slight  improvement.  In 
1906  x-rays  were  employed  in  1  case  which  had  been  treated  without 
success  with  antithyroidine  of  Moebius.  In  1907  a  meat-free  diet 
was  tried  on  ^  patients;  4  were  improved,  1  showed  only  very 
slight  temporary  improvement,  1  remained  negative.  lour  times 
Voit  used  phosphate  of  soda  and  phytin  treatment;  3  were  negative,  1 
improved,  and  1  markedly  improved.  Becker  went  to  the  trouble  to 
look  up  what  had  become  of  these  last  10  cases  since  1907.  I  le  succeeded 
in  getting  in  touch  with  only  7  of  them.  In  all  the  improvement  had 
remained  tin-  same.  They  were  more  or  less  materially  improved  but 
not  cured. 

As  reported  by  A.  Stenzel,  in  191  2,  54  eases  of  Basedow's  disease 
were  observed  in  Stintzing's  clinic  at  Jena.  Otto  says  10  of  these  mn 
severe  cases,  30  moderately  severe,  ami  14  were  of  the  milder  type.  Of 
these  70  per  cent,  wen  women  and  30  per  cent.  men.  I  hese  cases  were 
treated  medically,  according  to  the  newer  procedures,  for  at   least   six 


410 


TREATMENT  OF  GRAVES'  DISEASE 


weeks.  If  at  the  end  of  this  time  the  patients  did  not  show  improvement, 
they  were  transferred  for  surgical  treatment.  Eight  of  these  cases,  or 
about  15  per  cent.,  were  able  to  resume  their  work  after  treatment  for 
an  average  period  of  two  months.  Of  these  8  cases,  7  were  mild  and  1 
moderately  severe.  In  all,  however,  there  was  a  typical  Basedow  com- 
plex, the  cardinal  symptoms  all  being  frankly  present.  Twenty-one 
cases  or  about  39  per  cent,  were  improved — 2  of  these  being  mild  forms, 
15  moderately  severe,  and  4  severe.  Nineteen  cases,  about  one-third 
of  the  whole  number,  resisted  all  medical  treatment.  Among  these  were 
3  mild  cases,  12  moderately  severe  cases,  and  4  of  the  severe  type. 


Medical  Cases. 


Name. 
Williams    . 


Baruch 


White 
Cheadle  . 
Thompson 
Von  Graefe 
Von  Dusch 
Buschan  . 
Charcot  and 

Williamson 
Ord  and  Mackenzie 
Murray 
Vetlesen    . 
Frankl-Hochwart 


remaining 


Lichty 

Sainton 

Rogers 

Beebe 


No.  of  cases. 
3OO 


IO8 

not  given 
not  given 
not  given 
not  given 
not  given 


56 
40 

34 
60 


35 
74 
119 


Kocher 

100 

78 

Syllaba 

51 

Voit-Becker    . 

61 

remaining   . 

60 

Otto     .      .      . 

54 

Williams    . 

23 

Cure, 
per  cent. 


56 


25.O 

fruste  forms 
unaffected 

25-71 


150 
objective 
10. o 
subjective 


1.65 


150 


Improvement, 
per  cent. 

60.O 

3i-5 

5-2 

able  to  work 

26.3 
partially  able 

19.4 


Rate  per  cent. 
Negative  results,         Death, 
per  cent. 


42.89 

58.5 

-41 . 66 

80.0 
15.0 


27 

0 

52 

94 

60 

0 

39 

0 

3i 

8 

10. o 

68.0 


714 


31-42 
8.0 

17.0 


22.0 

330 

7.84 

35-0 
35-° 


per  cent. 
IO. O 


19.4 
IO.O 

10.0 
12.0 

12.0 
I2.0 

25.0 
25.O 

20.58 


42.85 
4.O 

o 


o 
22.0 

17.64 


25.0 


RESULTS  OF  MEDICAL  TREAT M EXT  411 

In  general,  this  material  showed  that  not  only  cases  of  lighter  grade,  but 
also  of  severer  types,  were  not  amenable  to  medical  treatment.  In  the 
cases  in  which  antithyroids  (Moebius)  was  used,  no  good  results  were 
observed.  This  was  true  also  of  the  x-rays,  where  used.  In  a  large 
number  of  those  cases  in  which  medical  treatment  had  failed,  the 
symptoms  disappeared  after  operation. 

Conclusions. — How  eloquent  all  these  figures  are!  Do  thev  not  show 
that  one  thing  must  strike  us  forcibly,  namely,  that  medical  statistics 
are  utterly  insufficient:  It  is  true  that  once  in  a  while  internists  will 
report  one  or  two  cases  treated  successfully  with  medical  means,  but 
large  statistics  describing  in  extenso  their  cases,  their  immediate  and 
remote  results,  are  rare.  Let  us  hope  that  internists  will  in  the  future 
strive  to  set  forth  more  and  better  data.  The  little  there  is  of  these, 
however,  does  not  well  stand  comparison  with  surgical  statistics.  From 
them  it  appears  that  medical  treatment  is  far  less  efficient,  far  less  rapid 
in  results,  far  less  fertile  in  cures  and  improvements,  and  far  more  dan- 
gerous quoad  vitam.  As  the  time  goes  by  the  surgical  death-rate  is 
being  constantly  reduced.  So  long,  however,  as  we  shall  have  to  revert 
to  surgical  means  to  cure  thyrotoxicosis,  so  long  as  we  cannot  disregard 
the  heart  of  the  patient,  his  nervous  system,  his  thymus,  his  chromaffin 
system,  his  liver,  his  kidneys,  there  will  always  be  an  "unavoidable 
death-rate." 

It  is  remarkable  to  see  how  operative  success  improves  with  the 
increased  experience  of  the  surgeon.     For  instance: 


Kocher's  Cases. 

Y<:ir  i     i 

1902  59 

1906  167 

1910  376 

1911  167 

191 2  130 
1916  300 

Mayo's  C\ses. 

1^04  40                                               150 

1 907  no  8.0 
[QOQ  405  l  5 
1 1 )  1 1  1 000  3  . 7 
1912  o 


Death-rate, 

per 

cent. 

6 

•5 

5 

.0 

4 

.0 

2 

■  3 

1 

■5 

I 

.0 

412 


TREATMENT  OF  GRAVES'  DISEASE 


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RESULTS  OF  MEDICAL   TREATMENT  415 

Riedl  had  40  per  cent,  in  his  first  40  cases,  3.3  per  cent,  in  his  follow- 
ing 30  cases.  The  writer  had  8  per  cent,  death  in  his  first  series  of  100 
cases,  7  per  cent,  in  his  second  series  of  122  cases,  and  3.2  per  cent,  in 
the  following  series  of  100  cases,  and  no  death  in  the  last  series  of  137 
cases.  Crile  had  31.3  per  cent,  death  in  16  cases,  10  per  cent,  in  the 
following  30,  and  1.3  per  cent,  in  the  following  150  cases.  This  pro- 
gressive improvement  in  the  death-rate  is  not  so  much  dependent  upon 
the  improvement  in  technic  of  the  surgeon,  as  upon  the  increased 
experience  and  knowledge  of  the  disease,  upon  the  more  judicious 
selection  of  cases,  and  upon  a  better  comprehension  of  the  indications 
for  operation  in  each  given  case.  The  surgeon  learns  by  experience 
that  Basedow  patients  are  fragile,  that  they  have  no,  or  little  resistance, 
that  operations  must  be  proportioned  to  their  strength,  and  that  failure 
to  estimate  the  proper  amount  of  surgical  traumatism  which  the  patient 
can  stand  may  mean  death. 

When  Shall  We  Consider  a  Patient  as  Cured? — If  we  glance  over  the 
statistics,  either  medical  or  surgical,  we  are  struck  by  the  fact  that 
authors  have  a  different  way  of  appreciating  the  word  cure.  It  is  obvi- 
ous that  some  regard  as  cured,  patients  who  are  regarded  by  others  as 
only  improved,  and  vice  versa.  What  then  shall  wTe  understand  by  cure  ? 
If  by  cure  we  mean  the  complete  disappearance  of  objective  as  well  as 
subjective  symptoms,  in  other  words,  if  we  have  in  view  a  complete 
restitutio  ad  integrum,  cure  in  Graves'  disease  is  less  frequent  than  is 
admitted,  be  it  in  surgical  or  in  medical  cases.  The  degree  of  cure  will 
be  directly  proportionate  to  the  stage  of  the  disease  in  which  treatment 
is  undertaken.  Only  in  the  earl)'  stage  can  surgical  treatment  give  95 
per  cent,  or  even  100  per  cent,  of  subjective  as  well  as  objective  cure. 
When  once  the  disease  has  progressed  beyond  certain  limits,  when  it 
has  lasted  for  a  long  period  of  time,  or  when  the  organs  have  become 
anatomically  damaged,  the  patient  may  feel  subjectively  cured;  he 
may  be  able  to  resume  his  normal  activity,  yet  there  still  remain  some 
objective  symptoms,  as  possibly  some  enlargement  of  the  thyroid,  some 
glaring  look,  some  widening  of  the  palpebral  fissure,  possibly  some 
tremor,  or  some  occasional  tachycardia— all  stigmata  of  the  past  patho- 
logical process,  similar  in  some  respects  to  the  scars  left  by  smallpox. 
In  some  instances  we  shall  find  that  exophthalmos  still  remains  in  a 
more  or  less  marked  degree,  yet  the  patient  is  cured.  The  reason  is 
found  in  the  fact  that  because  the  globus  oculi  has  been  pushed  out  ot 
place  for  so  long  a  rime,  production  of  retrobulbar  connective  tissue  and 
fat  has  taken  place,  thus  preventing  the  eye  from  sinking  back  into  its 
former  position.  Exophthalmos  in  that  case  is  no  longer  a  thyrotoxic 
symptom,  but  has  become  an  acquired  condition.  I  he  patient  may 
therefore   be   regarded    as   cured.      In    other   instances    some    degree    01 


416  TREATMENT  OF  GRAVES'  DISEASE 

tachycardia  or  of  myocarditis  still  remains,  yet  the  patient  is  uncon- 
scious of  it,  he  is  putting  on  flesh  and  feels  well.  There,  too,  the  cardiac 
symptoms  are  no  longer  thyrotoxic  symptoms,  but  must  be  regarded  as 
an  acquired  pathological  condition.  In  short,  the  disease  has  subsided, 
yet  indelible  traces  of  it  still  remain.  These  patients  are  cured  just  as 
those  who  are  burned  are  cured;  the  active  process  is  extinguished,  but 
there  still  remains  the  "scar,"  which  in  a  more  or  less  marked  degree, 
according  to  its  extent  and  seat,  will  add  to  the  depreciation  of  these 
individuals.  They  are  cured  only  so  far,  but  the  anatomical  damages 
done  to  the  organs  remain. 

It  is  to  be  desired  that  this  word,  cure,  applied  to  Graves'  disease, 
for  the  sake  of  clearness  and  discussion,  be  standardized.     It  might  be 
well  to  classify  our  results  in  the  following  manner: 
i.   Complete  cure; 

2.  Subjective  cure; 

3.  Great  improvement; 

4.  Moderate  improvement; 

5.  Failures; 

6.  Made  worse. 

1.  Completely  cured  are  the  ones  in  whom  restitutio  ad  integrum  has 
taken  place.  No  objective  or  subjective  symptoms  remain  as  a  living 
witness  of  the  past  pathological  process.  The  patient  has  regained  his 
former  health. 

2.  Subjectively  cured  are  those  who  subjectively  feel  well,  are  able  to 
resume  their  normal  activities,  and  are  able  to  stand,  emotional  as  well 
as  physical,  strain  without  undue  reaction.  There  may  be,  of  course, 
some  occasional  tachycardia,  some  occasional  nervousness,  some  occa- 
sional tremor;  they  may  still  show  some  thyroid  hyperplasia,  some  mod- 
erate degree  of  exophthalmos,  some  widening  of  the  palpebral  fissure, 
etc.  These  symptoms,  however,  are  not  sufficiently  troublesome  to  pre- 
vent the  patient  from  leading  a  life  of  normal  activity  and  usefulness. 
These  patients  rated  at  a  "market  value"  might  be  considered  as  depre- 
ciated; the}',  however,  are  unconscious  of  this  depreciation.  They  are 
subjectively  cured. 

The  other  divisions  adopted:  greatly  improved,  failures,  made  worse, 
are  self-explanatory. 

Unfortunately  too  many  medical  men  as  well  as  surgeons  content 
themselves  in  giving  their  immediate  results  and  do  not  bother  about 
noting  their  remote  results.  It  must  be  said,  however,  that  surgeons 
have  felt  such  a  necessity  more  keenly  than  medical  men,  and  in  conse- 
quence a  great  number  of  them  have  sought  to  fill  the  gap. 

We  sometimes  hear  of  medical  men  advising  against  operation 
because  injury  to  the  inferior  laryngeal  nerve,  or  to  the  parathyroids, 


MEDICAL  TREATMENT  417 

mav  occur,  or  surgical  intervention  fails  to  bring  about  a  cure,  or  relapses 
after  operation  are  sometimes  seen,  or  because  sometimes  myxedema  is 
the  sequela  of  the  surgical  treatment. 

In  answer  to  these  objections  I  will  say  that  with  the  improvement 
of  our  technic,  injuries  to  the  inferior  laryngeal  nerve  or  parathyroids 
are  rare.  When  they  do  occur  they  are  not  necessarily  serious  compli- 
cations. Furthermore,  that  surgical  treatment  is  not  always  successful, 
no  one  will  deny.  But  the  same  result  is  truer  for  the  medical  treatment. 
There  are  cases,  few  in  number  fortunately,  but  nevertheless  existing, 
which  derive  little  or  no  benefit  from  an  operation.  As  a  rule  this  is 
due  to  the  fact  that  the  case  was  beyond  repair,  or  that  the  operation 
has  been  insufficient;  the  case  then  belongs  to  the  ones  regarded  by 
Kocher  as  "nicht  fertig  operiert."  However,  if  the  patient  is  reoperated, 
then  the  results  become  very  much  more  satisfactory,  and  absolute  cure 
mav  follow.  In  some  other  cases  success  may  fail  to  respond  when  the 
thyroid  is  not  the  primary  cause,  as  in  the  case  of  von  Haberer's;  there 
thyroidectomy  had  been  of  no  avail,  whereas  thymectomy  was  followed 
by  a  marvelous  cure. 

It  is  said  that  there  are  cases  which  are  made  directly  worse  by  the 
operation;  these  are  rare  indeed.  I  have  never  observed  any  in  my  own 
experience.  To  be  sure  relapses  are  met  with  once  in  a  while,  but  the 
same  is  far  more  true  for  the  medical  treatment. 

We  see  sometimes,  fortunately  rarely,  patients  who  have  been  oper- 
ated upon  gradually  show  symptoms  of  hypothyroidism.  But  the  same 
is  true,  too,  for  medical  treatment.  Have  we  not  said  more  than  once 
that  a  thyrotoxic  patient  left  alone,  unless  he  recovers  or  dies  from  the 
disease,  is  logically  destined  to  become  myxedematous?  Some  intern- 
ists accuse  surgeons  of  considering  as  cured  patients  who  are  only 
improved,  and  of  not  waiting  long  enough  before  publishing  their  results. 
The  same  can  be  said  for  internists;  they,  too,  consider  as  cured  cases 
which  are  only  improved,  and  they,  too,  have  relapses.  How  often  do 
we  not  see  Basedow  patients  who  have  been  treated  several  tunes  by 
several  different  internists  and  each  time  have  been  discharged  as  cured, 
come  and  sick  surgical  help? 

MEDICAL    TREATMENT. 

Rest  Cure.  Rest  cure  is  certainly  the  Inst  among  all  the  medical 
means  we  have  at  hand  to  combat  Graves'  disease.  It  is  tin-  one  which 
was  already  used  by  our  forerunners  in  medicine;  in  fact,  it  is  as  old 
as  the  world  itself.  Nature  applies  it  constantly;  nature  "rests"  during 
tin-  winter  from  lur  spring  and  summer  activities.  When  a  muscle  has 
been  driven  too  long,  it  automatically  "rests"  in  order  to  recuperate. 

27 


41S  TREATMENT  OF  GRAVES'  DISEASE 

Sleep  is  only  a  forced  "rest."  In  medicine,  "rest"  is  a  panacea:  the  best 
medicine  for  an  overburdened  stomach  is  rest;  rest  is  an  essential  factor 
for  the  recuperation  of  an  overdriven  heart;  it  is  a  necessity  for  a  wrecked 
nervous  system.  No  wonder  then  that  it  was  applied  to  relieve  thyro- 
toxicosis. 

There  is  a  great  deal  of  truth  in  what  Crile  says,  "If  the  brain  could 
enter  into  a  state  of  actual  hibernation  like  the  bear,  it  [i.  e.,  thyrotoxi- 
cosis] would  certainly  be  cured;  but  unhappily  the  knowledge  of  the 
gravity  of  the  disease  itself  becomes  one  of  the  psychic  excitants  which 
aggravate  the  disease,  the  entanglement  frequently  becomes  hopeless, 
and  like  the  Gordian  knot,  must  be  cut."  I  am,  however,  not  convinced 
that  "brain  hibernation"  alone  would  suffice  to  bring  about  a  cure.  We 
often  see  patients  whose  nervous  disturbances  are  only  second  to  their 
other  symptoms;  these  patients  are  usually  moderately  nervous,  they 
sleep  well,  yet,  sleep,  which  is  in  itself  a  hibernation,  makes  little  or  no 
difference  in  their  condition.  During  sleep  their  organism  is  still  being 
driven  at  top  speed,  the  fire  does  not  subside  even  partially.  All  this  is 
so  because  the  brain  only  "hibernates"  and  not  the  other  organs,  espe- 
cially the  thyroid.  If  the  entire  organism  could  hibernate,  only  then 
would  we  have  a  cure.  From  this  it  follows  that  rest  is  only  an  indirect 
means  of  treating  thyrotoxicosis;  it  does  not  attack  the  causal  factor 
itself,  namely,  the  thyroid,  but  influences  it  most  by  an  indirect  route, 
the  nervous  system. 

In  order  to  be  therapeutic,  rest  must  be  complete;  it  must  conse- 
quently be  mental  as  well  as  physical.  Here,  again,  it  is  difficult  to  set 
down  hard-and-fast  rules.  The  majority  of  patients  will  do  better  far 
away  from  their  ordinary  surroundings.  For  some  the  best  place  is  in  a 
sanitarium  or  hospital;  others  will  find  in  a  sojourn  in  the  country  or 
woods  more  complete  freedom  from  mental,  emotional,  and  physical 
exertion.  These  patients  should  stay  and  sleep  out  of  doors  day  and 
night  as  much  as  possible.  A  sojourn  in  a  moderate  altitude,  iooo  to 
2500  feet,  is  far  more  beneficial  to  them  than  the  seashore,  where  the 
majority  of  these  patients  are  made  distinctly  worse.  Careful  inquiry 
will  often  elicit  some  particular  etiological  factor  such  as  overwork, 
worry,  disappointment,  etc.,  which  has  been  instrumental  in  fomenting 
the  disease.  This,  of  course,  so  far  as  possible  must  be  eliminated. 
Talkative  friends  must  be  rigidly  excluded.  The  same  is  true  for  mem- 
bers of  the  family  from  whose  petty  disputes  and  vexatious  interfer- 
ences, as  Beebe  expresses  himself,  the  patient  at  times  stands  sorely  in 
need  of  protection.  Only  one  or  two  sympathetic  and  congenial  visi- 
tors may  be  allowed  to  visit  for  a  short  time  occasionally,  and  indeed 
just  as  a  distraction;  solitude  must  not  be  allowed  to  become  too  heavy 
to  bear.     It  must  never  be  forgotten  that  thyrotoxic  patients  are  highly 


MEDICAL   TREATMEXT  419 

sensitive  and  often  react  with  a  veritable  thyrotoxic  explosion  to  some 
trivial  annovance.  The  moral  comfort,  the  persuasive,  although  firm 
attitude  of  the  physician,  and  the  implicit  confidence  of  the  patient  in 
him,  are  necessary  conditions  for  success. 

Thus  it  will  readily  be  seen  that  the  true  "rest  cure"  is  difficult  to 
obtain.  Onlv  people  of  means  can  follow  a  real  "rest  cure"  and  although 
with  them  expense  is  a  secondary  matter,  even  they  as  time  goes  by, 
after  months  and  possibly  years  have  elapsed  and  the  much-longed-for 
cure  is  still  far  away,  become  discouraged,  worried,  and  impatient;  the 
"rest  cure"  becomes  a  burden  to  them.  Under  such  circumstances 
benefit  can  no  longer  be  expected  from  rest. 

If  this  is  true  for  the  rich  class,  how  much  truer  is  it  for  the  working 
class  ?  The  necessities  of  life  are  imperative  with  them.  They  must 
make  their  living;  they  may  even  have  large  families  to  take  care  of,  or 
the)'  may  have  a  sick  husband,  father,  or  mother,  to  support  while  they 
have  little  or  nothing  to  live  upon  except  what  they  make.  How  would 
you  expect  them  to  "rest?"  Indeed,  they  will  obey  your  orders  and  try 
to  rest,  but  when  after  three,  five,  eight  weeks  of  rest,  they  see  no  improve- 
ment, when  they  possibly  see  that  the  condition  is  getting  worse,  when 
their  financial  means  are  becoming  exhausted,  or  when  finally  they  real- 
ize that  this  "rest  cure"  may  last  months  or  years,  and  that  very  likely 
at  the  end  of  that  time  they  will  have  to  be  operated  upon  anyway,  the)' 
give  up  in  despair  and  indeed,  no  one  can  blame  them  for  it.  "Rest 
cure"  for  them  is  impossible;  it  is  illusory.  Under  such  conditions,  rest 
cure  is  only  good  as  being  preparatory  to  surgical  treatment,  and  not 
at  all  as  a  curative  means. 

Medication. — So  long  as  there  is  no  specific  medicine  for  Graves' 
disease  the  little  which  can  be  used  is  based  purely  upon  symptomatic 
indications. 

Digitalis  and  strophanthus  have  been  used  extensively.  W  hen 
organic  cardiac  disturbances  are  present  this  medication  has  shown 
itself  very  beneficial.  \\  hen  the  disturbances  are  purely  functional 
little  or  no  benefit  has  been  obtained.  Not  infrequently  it  has  proved 
harmful. 

Nervousness  and  insomnia  are  treated  with  bromides,  aconite, 
tnonal,  sulfonal,  chloral,  veronal,  and  baldnan. 

Belladonna   and  atropin  are  often   beneficial  in  excessive  swearing. 

Antipyrin,  salicylate  of  soda,  and  aspirin  have  been  used  when-  there 
is  some  fever,  neuralgic  pain,  and  especially  acute  articular  rheumatism. 

Arsenic  is  oftentimes  not  well  tolerated,  vel  ir  is  a  valuable  remedy. 
Ir  can  be  given  under  the  form  of  Fowler's  solution,  of  pills  (pillulae 
asiaticae),  or  of  cacodylate  of  soda  subcutaneously.  Iron  finds  little 
indication. 


420  TREATMENT  OF  GRAVES'  DISEASE 

Glycerophosphate  of  soda  has  sometimes  given  excellent  results. 
Phosphate  of  soda  has  been  recommended  by  Kocher.  It  must  be  given 
in  large  doses  6  to  8  grams  a  day,  since  only  a  small  proportion  of  it 
is  absorbed. 

Salts  of  quinine,  according  to  Marquette,  act  upon  the  sympathetic 
and,  according  to  Huchard  and  Lanceraux,  have  a  vasoconstrictive 
effect  upon  the  thyroid.  What  in  the  Middle-west  of  our  country  is 
known  as  the  "Forcheimer  treatment"  is  based  upon  the  use  of  hydro- 
bromate  of  quinine  and  ergotin. 

1^ — Quinine  hydrobromate 5  grains. 

Ergotin I  grain. 

D.S. —  I  hree  or  four  times  a  day. 

Forcheimer  was  led  to  use  the  quinine  by  noting  the  favorable  action 
on  an  individual  patient  and  the  fact  that  "Jesuit's  bark"  had  been 
advocated  in  the  treatment  of  goiter.  Ergotin  was  used  on  the  theory 
that  it  influenced  the  size  of  the  bloodvessels.  The  use  of  either  of  these 
medicines  in  exophthalmic  goiter  is  empirical,  and  neither  one  is  par- 
ticularly indicated.  It  is  nevertheless  a  fact  that  some  patients  have 
improved  decidedly  and  rapidly  with  that  form  of  treatment.  In  many 
others,  however,  the  effect  is  scant  and  not  lasting,  or  totally  negative. 

For  itching  the  following  formula  is  sometimes  of  value: 

1$ — Carbolic  acid io.o 

Acetic  acid 200.0 

Aq.  dest ' 790.0 

M.D.S. — For  external  use. 

Diet. — A  simple,  good,  wholesome,  varied  diet  with  plenty  of  every- 
thing is  much  the  best.  Wines,  tea,  coffee,  red  meats,  and  highly  sea- 
soned food  should  be  avoided.  Chicken  and  fish  may  be  allowed.  Some 
patients  do  well  with  a  diet  rich  in  carbohydrates  and  fats.  Vegetables, 
especially  the  leguminous  plants,  are  very  beneficial,  not  only  on  account 
of  their  alimentary  quotient  and  influence  upon  the  motility  of  the  intes- 
tines, but  also  on  account  of  their  mineralizing  properties.  This  latter 
feature  is  of  importance  since  we  know  that  Basedow  patients  often 
eliminate  great  amounts  of  mineral  salts,  especially  phosphates  and  cal- 
cium salts.  Water  must  be  taken  plentifully.  Meals  should  be  taken 
regularly,  three  times  a  day,  with  nothing  between  times.  With  some 
patients,  however,  it  may  be  deemed  necessary  to  push  the  feeding  by 
increasing  the  number  of  meals.  Great  care  should  be  taken  not  to 
upset  the  stomach.  Sometimes  large  quantities  of  milk,  kephir  or 
zoulac,  three  or  four  quarts  a  day,  prove  exceedingly  beneficial.  Often, 
however,  this  fluid  diet  is  not  well  tolerated  and  causes  stomach  dilata- 


MEDICAL  TREAT M EXT  421 

tion,  hyperacidity,  indigestion;  in  that  case  the  object  of  the  diet  is 
defeated.  As  a  general  principle,  our  aim  should  be  to  feed  the  patient 
to  the  utmost  with  the  least  tax  upon  the  digestive  apparatus. 

Hydrotherapy. — Hydrotherapy  is,  too,  an  excellent  adjuvant  of  the 
medical  treatment.  The  exact  form  in  which  it  must  be  used  depends 
upon  the  patient.  Most  patients  react  well  to  baths,  provided  these  are 
of  moderate  temperature.  Such  baths,  as  a  rule,  have  a  quieting  effect 
upon  the  nervous  system,  enable  the  patient  to  sleep  better,  and  tonify 
the  musculature.  Some  other  patients  will  do  better  by  taking  a  warm 
bath  first,  followed  by  a  cold  spray  or  douche.  When  vascular  symptoms 
are  greatly  developed  in  the  thyroid,  and  when  tachycardia  is  very 
marked,  ice-bags  applied  on  the  neck  and  an  ice-cap  over  the  heart  are 
often  able  to  reduce  the  activity  of  the  thyroid  and  to  mitigate  the 
severity  of  the  cardiac  symptoms. 

So  far  as  bath  resorts  are  concerned,  although  a  number  of  them  are 
advertised,  especially  in  Europe,  as  highly  beneficial  to  Basedow  patients, 
none  of  them  has  won  fame  as  "specific."  Whenever  I  am  called  upon 
to  give  advice  in  this  respect,  I  always  try  to  send  my  patients  to  regions 
where  the  water  is  notoriously  goitengenous  in  the  hope  that  it  will 
calm  down  the  high,  hyperactive  epithelium  of  the  thyroid  gland.  The 
well-known  benefit  that  Basedow  patients  derive  from  a  sojourn  in 
mountainous  and  goiterigenous  regions  of  Switzerland  may  very  well 
be  attributed  to  this  fact. 

Electrotherapy. — Electric  treatment  may  be  general  or  local.  The 
general  treatment  portends  to  quiet  the  nervous  system,  and  to  facilitate 
the  elimination  of  thyroid  toxins.  The  local  treatment  tends  to  influence 
di rectl\'  the  thyroid,  sympathetic,  and  bulbar  centers. 

General  Treatment. — Vigouroux  divided  Basedow's  disease  into  two 
large  categories:  those  which  have  a  retarded  metabolism,  and  those 
winch  have  an  accelerated  one.  According  to  him  electric  treatment 
should  not  be  applied  to  the  second  class,  as  it  will  only  tend  to  exaggerate 
the  symptoms,  especially  tachycardia,  and  nervousness;  on  the  con- 
trary, those  who  have  a  retarded  metabolism  will  be  greatly  benefited 
by  electric  treatment  under  the  forms  of  static  baths  lasting  from  ten 
to  twenty  minutes  each  time.  Baths  of  high  frequency  can  be  given 
and  their  efficacy  is  well  supported. 

Local  Treatment.—  \  igouroux  employs  the  faradic  treatment  applied, 
ist,  on  the  carotid  region;  2d,  on  the  eyes;  jd,  on  the  goiter  itself;  and 
4th,  on  the  cardiac  region.  The  treatment  produces  diminution  of  the 
nervous  excitement  and  favors  sleep. 

Galvanic  Treatment.  In  the  last  few  years  the  galvanic  treatment 
has  become  classical.  A  large,  well-padded  electrode,  *o  to  120  sq. 
cms.,  is  connected  with  the  negative  pole  while  another  electrode  from 


422  TREATMENT  OF  GRAVES'  DISEASE 

150  to  200  sq.  cms.  is  placed  on  the  superior  portion  of  the  spinal  col- 
umn and  put  in  communication  with  the  positive  pole.  The  current 
must  be  graduated  with  a  rheostat  and  brusque  variations  avoided. 
Thirty  to  60  milhamperes  are  used.  The  treatment  lasts  from  ten  to 
thirty-five  minutes  every  day. 

For  M.  Chartier,  the  galvanofaradization  of  the  thyroid,  especially 
at  its  vascular  poles,  of  the  heart,  and  of  the  vagosympathetic  system  is 
the  method  of  choice.  A.  R.  Rainear  gives  the  preference  to  the  con- 
tinuous electric  current.  This  form  of  treatment  requires  a  great  deal 
of  experience  and  its  intensity  must  be  in  direct  proportion  to  the  toler- 
ance of  the  patient,  consequently  the  amperage  will  vary  with  each 
given  case.  The  dimensions  and  nature  of  the  electrode,  as  well  as  the 
polarity  to  be  employed,  are  important.  The  method  of  choice  is  to  place 
the  cathode  upon  the  thyroid;  this  electrode  must  be  of  appropriate 
size  and  nature.  When  such  is  the  case  the  intensity  of  the  current  may 
run  up  to  70  milhamperes.  The  current  must  be  started  progressively 
and  stopped  the  same  way,  otherwise  pain  will  follow.  The  electrode 
used  for  the  electric  treatment  of  the  eyes  is  of  cup-shaped  form  and 
must  be  closely  adapted  to  the  eyes.  It  is  filled  with  moistened  cotton 
and  the  milliamperage  must  be  very  low. 

Electrolysis  could  be  employed  as  a  means  of  reducing  the  size  of 
the  gland,  but  is  painful,  requires  a  great  number  of  applications,  leaves 
a  scar,  and  finally  may  cause  respiratory  disturbances  on  account  of 
connective-tissue  degeneration  of  the  gland. 

In  conclusion  it  may  be  said  that  electric  treatment,  whatever  its 
form  may  be,  for  Graves'  disease  has  often  a  beneficial  effect,  especially 
when  combined  with  other  medical  measures.  Its  results,  however,  are 
not  lasting  and  are  rarely  curative.  The  condition  generally  relapses 
as  soon  as  the  treatment  is  stopped. 

Radiotherapy. — X-ray  treatment  has  a  sedative  and  soothing  effect 
upon  the  nervous  system  of  the  patient.  It  ameliorates  the  cardiac 
condition  and  diminishes  the  goiter,  but  its  effects  are  inconsistent  and 
not  lasting.  In  advanced  cases  where  other  medical  means  fail  to  bring 
about  sufficient  amelioration  to  permit  some  surgical  interference,  and 
when  the  case  is  steadily  growing  worse,  x-rays  may  be  used  to  bring 
about  a  shrinkage  of  the  thyroid  gland  and  a  sufficient  diminution  of  the 
thyrotoxic  symptoms  to  allow  surgery  to  take  place.  This  treatment 
has,  however,  the  great  disadvantage  of  creating  many  adhesions  around 
the  gland,  thus  rendering  the  operation  bloody  and  difficult.  It  is,  too, 
a  difficult  matter  to  estimate  the  proper  duration  of  this  treatment  and 
the  dosage  suitable  to  every  case.  If  one  is  guided  only  by  the  ameliora- 
tion of  the  symptoms,  the  treatment  may  very  well  last  so  long  that, 
subsequently,  hypothyroidism  will  follow. 


MEDIC  A  L   TREA  TMEXT 


423 


Treatment  with  X-rays. 


Name  anl  year. 


Remarks. 


1906 
Sklodowski.  J.,   Deutsch.   med.       1 
\\  chnschr.,  1906,  xxxii,  1340. 

1911-12 
Rinniger,  E.  M.,  Northwest  M.       4 
1911-12,  iii,  44. 

1913 
Boumann,  H.  A.  H.,  Jour.-Lan-      2 
cet,  Minn.,  1913,  xxxiii,  425. 
1906 
PfeifFer,  C,  Beitr.  z.  klin.  Chir.,      51      51 
1906,  xlviii,  367. 
1907 
Beck,    C,     New    York     Med.,        8        8 
Monstschr.,   1907,  xix,  281. 
1909 
Taylor,  \\  .  J.,  Am.  Surg.,  1909, 
xlix,  578. 

1910-11 

Freund,  L.,  Arch.  Roentg.  Ray,      23      17 
1910-11,  xv,  13. 
1911-12 
Scott,  J.    N.,  Jour.    Mo.    State      11      10 
Med.  Assn.,  1911-12,  viii,  151 

1912 
Storey 
I looten 
Hooten 

1913 
Blitstein,     M.,     Prakt.     Aerzt.,        3        3 

1913,  liii. 
I  urner,    D.,    Lancet,    London,        4        4 
1913,  ii,  924. 

1914 
Birdsall,    k.,    New    York   Med.        3        3 

Jour.,  xcix,  1032. 
Leonard,  C.  L.,  Ibid.,  579.  4        4 

1  ,1'. 
kislier,    Ugeskrift   for  Laeger.       94 


Case,   Iowa   Stan-   Med.  Jour.       30 
Rugles,  Calif.  Jour,  of  Mtil.  24 


41 
14 

17 


14 
10 

7 


1 

15 


27 


20 
10 

4 
4 
2 

4 

3 

3 

79 


Treated  by  v-rays.  Symp- 
toms relieved  but  patient 
not  cured  in  six  months. 


22     Treated  by  .v-rays. 


Treated  by  v-rays. 


Treated   by  .v-rays.      Was 
made  worse. 


3      I  reated  by  .v-rays. 


Treated    by  .v-rays.      One 
subsequently    operated 
upon. 


Private  patients. 
Hospital  cases. 


Seymour,     Boston     Med.    and     80 
Surg.  Jour. 


1  reated  bv  x-rays. 

I  reared  by  radium  pre- 
ceded by  v-rays. 

I  reated   by  v-rays.      (  Inly 
relieved  symptomatica II v. 
I  reared  by  .v-ravs. 

Exophthalmos    remained 
refractory. 

CI. inns  results  as  i:ood  as 
can  be  obtained  by  sur- 
gery. 

Improved  as  regards  nerv- 
ous sweating,  weight,  and 
sleeplessness. 

Balance  improA  ed. 


424 


TREATMENT  OF  GRAVES'  DISEASE 


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426  TREATMENT  OF  GRAVES'  DISEASE 

Serotherapy. — Two  methods  have  been  in  use;  the  one  intending  to 
neutralize  the  thyroid  secretion  in  the  organism  itself,  and  the  other, 
by  the  use  of  a  thyrotoxic  serum,  aiming  to  diminish  the  secreting  sur- 
face of  the  thyroid  or  to  destroy  a  portion  of  its  secreting  elements.  The 
first  method  is  called  antithyroid  chy mother apy,  and  the  second,  thyro- 
toxic serotherapy. 

Antithyroid  Chymotherapy. — Many  attempts  have  been  made  in 
recent  years  to  alleviate  the  symptoms  of  Graves'  disease  by  giving  the 
patient  milk,  serum,  or  dried  blood  taken  from  totally  thyroidectomized 
animals.  The  principle  underlying  this  therapeutic  measure  is,  that 
after  thyroidectomy,  substances,  or  better  antibodies,  accumulate  in  the 
blood  or  milk  of  the  thyroidectomized  animals.  When  administered  to 
a  thyrotoxic  patient,  these  antibodies  neutralize  in  some  way  or  another 
the  excess  secretion  of  the  thyroid.  It  was  suggested  by  Hunt  that  the 
results  obtained  with  the  milk  of  the  thyroidectomized  animals  were 
due  to  the  milk  diet  per  se  and  not  to  the  formation  of  antibodies. 
Edmunds  and  Trendelenburg  concluded  from  their  experiments  that  in 
thyrotoxic  animals  toxic  substances  accumulated  in  the  blood  and  milk, 
and  that  these  substances  instead  of  being  antagonistic  to  the  thyroid, 
had  a  synergistic  action;  while  Hunt  believed  that  the  blood  of  thyro- 
toxic animals  contained  substances  which  aroused  the  thyroid  gland  to 
increased  activity,  as  is  shown  by  the  acetonetrile  test.  This  suggestion 
is  in  harmony  with  the  conclusion  of  Edmunds,  who  found  that  the 
administration  of  milk  of  totally  thyroidectomized  goats  to  rats  fed 
with  thyroid  hastened  the  death  of  the  rats. 

The  various  chymotherapeutic  agents  are:  in  France,  hematoethy- 
roidin  of  Hallion,  which  is  the  total  blood  of  thyroidectomized  horses; 
in  Germany,  the  Moebius  antithyroidin  of  Merck,  which  is  the  serum  of 
thyroidectomized  sheep,  and  which  can  be  obtained  either  in  dried  or 
liquid  form,  and  the  rhodagen  of  Burgardt  and  Blumenthal,  which  is  the 
dried  milk  of  thyroidectomized  goats;  in  England  and  America,  the 
thyroidectine  of  Parke,  Davis  &  Co. 

All  these  various  chymotherapeutic  products  are  used  per  os  and 
not  subcutaneously  or  intravenously  on  account  of  the  symptoms  of 
intoxication,  and  especially  on  account  of  anaphylaxis,  which  they  are 
hable  to  cause. 

The  results  from  such  methods  are  variable,  most  of  them  having 
resulted  in  failures.  The  amelioration  obtained  is  usually  only  tem- 
porary and  relapses  as  soon  as  the  treatment  is  ceased;  furthermore,  the 
treatment  is  of  long  duration.  Cases  of  hypothyroidism  in  connection 
with  their  use  have  been  observed  by  Dunz,  Diing,  Murray,  Blumen- 
thal and  Pitt.  It  is  not  said,  however,  that  this  hypothyroidism  was 
caused  by  chymotherapeutic  agents    themselves,  but    may    have    been 


MEDICAL  TREATMENT  427 

the  natural  result  of  the  prolonged  overactivity  of  the  gland  resulting 
finally  in  hypoactivity. 

Thyrotoxic  Serotherapy. — As  said  before,  this  method  aims  to  dimin- 
ish the  secreting  surface  of  the  thyroid  by  inhibiting  or  destroying  a 
portion  of  its  secreting  cells.  The  theory  is  based  upon  the  researches 
of  Bordet  and  MetchnikofF  who  have  found  that  if  repeated  injections 
of  crushed  products  of  an  organ  such  as  the  liver,  the  kidnev,  etc.,  are 
injected  into  an  animal,  there  appear  in  the  serum  of  this  animal 
substances  which  exert  an  elective,  destructive  influence  upon  the 
organ  similar  to  the  one  from  which  they  originate.  The  serum  has 
become  cytotoxic  for  that  organ;  since  we  have  a  hepatoxic,  a  nephro- 
toxic, and  surrenotoxic  serum,  we  have,  too,  a  thyrotoxic  serum. 

The  first  researches  were  made  simultaneously  in  the  same  vear  bv 
various  physiologists  such  as  Sartinara,  Gontscharukow,  Mankowsy. 
The  first  attempt  with  cytotoxic  serotherapy  in  man  was  made  bv 
Murray.  Rogers  and  Beebe,  however,  have  done  the  most  extensive 
work  in  that  line.  In  Beebe's  opinion  the  dose  used  for  therapeutic 
purposes  is  not  actively  cytotoxic,  the  purpose  of  the  treatment  being 
to  relieve  the  toxins  and  not  to  cause  an  immediate  destruction  of  the 
gland;  consequently  he  regards  it  as  antitoxic. 

The  thyrotoxic  serum  is  very  apt  to  cause  anaphylaxis,  either  local 
or  general.  As  Beebe  says,  the  patient  complains  of  intense  pain  in  the 
back,  and  experiences  a  sense  of  suffocation.  The  skin  becomes  flushed 
and  itches  intensely;  the  patient  is  nauseated,  may  vomit;  and  syncope 
may  follow.  However,  the  whole  disturbance  subsides  quickly  and  the 
patient,  aside  from  being  frightened,  is  soon  all  right  again.  These 
symptoms  are  especially  apt  to  occur  when  erroneously  the  injection 
has  been  made  intravenous.  Phenomena  of  local  anaphylaxis  are  charac- 
terized by  swelling  of  the  arms,  pain,  redness,  and  erysipelatous-like 
eruptions. 

The  results  obtained  with  such  therapeutic  methods  are  exceed- 
ingly variable  and,  as  seen,  are  not  devoid  of  danger.  According  to 
Lenormant,  sudden  deaths  have  followed  this  form  of  treatment. 
Furthermore,  the  treatment  is  painful,  long  and  expensive,  and  the 
serum  is  not  always  easilv  obtainable.  In  the  estimation  of  its  most 
active  promoters,  this  "specific  serum"  is  not  "specifically  curative," 
inasmuch  as  it  must  be  backed  up  by  medical  or  surgical  treatment. 
It  is  an  adjuvant  of  either  medical  or  surgical  means.  The  theory  upon 
which  it  is  based  is  of  extraordinary  interest,  u\m\  may  some  day  give  us 
the  solution  of  our  problem. 

Polyglandular  Medication.  Ovarian  and  testicular  opotherapy  have 
been  used  with  some  success  in  certain  cases  and  with  failures  in  others. 
I  hose   cases   winch    were    successful    wen-    the   ones    in    which    Basedow's 


428  TREATMENT  OF  GRAVES1  DISEASE 

disease  was  seemingly  dependent  upon  disturbances  of  the  ovarian  func- 
tion either  at  the  time  of  puberty,  menopause,  or  pregnancy.  On  the 
other  hand,  in  many  such  cases  the  results  remained  negative. 

Thymus  Opotherapy.- — The  thymus  was  used  for  the  first  time,  and 
accidentally  at  that,  in  1895  by  Owen  who  had  prescribed  for  his  patient 
fresh  thyroid.  The  doctor  saw  afterward  only  that  the  butcher  had 
mistaken  the  thymus  for  the  thyroid,  yet  the  result  of  its  use  was  bril- 
liant. Since  then  thymic  opotherapy  has  been  used  with  marked  suc- 
cess in  some  cases  and  again  with  total  failure  in  others.  The  thymuses 
of  calves  and  sheep  are  to  be  selected  when  this  method  is  resorted  to. 

Hypophysis  Opotherapy. — Hypophysis  opotherapy  has  been  used  to 
alleviate  the  symptoms  of  hyperthyroidism  with  the  most  varying 
results.  When  effective  it  alleviates  the  tremor,  digestive  troubles, 
sweating  and  hot  flashes;  tachycardia  diminishes  and  the  general  condi- 
tion of  the  patient  improves.    The  results,  however,  are  inconstant. 

Parathyroid  Opotherapy. — Parathyroid  opotherapy  was  used  with 
some  success  by  Monson;  the  case  was  markedly  improved,  but  relapsed 
as  soon  as  the  treatment  was  stopped. 

Adrenalin  has  been  used  without  great  success. 

Pancreas  Opotherapy  has  sometimes  proved  beneficial  in  the  fulmi- 
nating forms  of  hyperthyroidism  of  the  gastro-intestinal  type.  Often, 
however,  it  has  proved  a  failure.  I  have  employed  this  medication  with 
the  most  varying  results. 

Polyglandular  opotherapy  is  still  in  its  infancy;  more  trials  of  it 
should  be  made. 

Crotti's  Treatment  for  Exophthalmic  Goiter. —  During  the  past  year  I 
have  been  using  the  following  formulae  with  very  good  success.  In  a 
number  of  cases  the  results  were  remarkable;  in  others,  however,  they 
were  negative.  I  called  the  first  set  of  tablets  Thyrotoxic  Goiter  Tablets, 
the  second,  Polyglandular  Tablets. 

Toxic  Goiter  Tablets. 

Sodium  arsenate 0.001 

Sodium  phosphate 0.12 

Salol 0.1 

Sodium  bromide 0.05 

Sodium  bicarbonate 0.05 

Calcium  oxalate 0.05 

(Chocolate  coated) 

Polyglandular  Tablets 

Pituitary  gland  (desiccated) 0.05 

Suprarenal  gland  (desiccated)  U.  S.  P 005 

Pancreas  (desiccated) 005 

Corpora  lutea  (desiccated) 0.05 

(Chocolate  coated) 


MEDICAL  TREATMENT  429 

The  toxic  goiter  tablets  and  the  polyglandular  tablets  are  prescribed 
simultaneously.  The  patient  is  told  to  take  two  of  each  at  the  same 
time,  three  to  six  times  a  day. 

Like  the  simple  goiter  tablets  these  tablets  have  been  put  up  for  me 
by  the  Parke,  Davis  &  Co.  I  have  no  objection  to  having  any  other 
firm  put  them  up.     These  tablets  are  not  patent  medicine. 


CHAPTER   XXXIX. 

INDICATIONS   AND  CONTRA-INDICATIONS  FOR  SURGICAL 
TREATMENT  OF  EXOPHTHALMIC  GOITER. 

As  we  have  seen,  neither  medical  nor  medicinal  treatment,  nor  radio- 
therapy, nor  serotherapy,  is  able  to  compete  with  surgery  so  far  as 
results  are  concerned.  Their  results  are  inconstant,  incomplete,  and 
insufficient.     Surgical  treatment  is  the  method  of  choice. 

Too  often,  however,  medical  men  consider  surgical  operation  in 
Graves'  disease  as  a  means  of  last  resort.  They  wait  too  long.  They 
experiment  with  too  many  medicaments.  In  the  meantime  the  disease 
progresses  beyond  their  control;  the  organs  become  vitally  damaged, 
and  the  outcome  becomes  more  than  dubious.  Only  then,  they  call  in 
the  surgeon  to  see  what  can  be  done:  and  like  Pilate,  they  too,  wash 
their  hands  of  it  all.  It  must  be  emphatically  proclaimed  that  this  way 
of  doing  is  unfair;  unfair  to  the  patient,  because  he  loses  his  best  chances 
of  a  complete  cure;  unfair  to  the  surgeon,  because  his  efforts  cannot  be 
crowned  with  the  success  they  should;  and  unfair  to  future  patients. 
How  often  do  we  not  see  patients  in  the  early  development  of  their 
disease  frightened  away  from  an  operation  because  a  hopelessly  lost 
case  has  been  given  the  "last  chance,"  the  one  of  operation,  and  has 
died  ?  On  that  account  an  early  case,  which  otherwise  would  have 
accepted  an  operation  and  would  have  been  cured  bv  it,  will  hesitate, 
procrastinate,  and  thereby  lose  precious  time.  Only  when  the  case  is  too 
far  advanced  for  assured  success  will  an  operation  be  sought. 

Since  it  is  a  recognized  fact  that  surgical  treatment  can  be  beneficial 
or  curative,  and  indeed  this  has  been  abundantly  demonstrated,  why 
wait  so  long  before  calling  in  a  surgeon  ?  On  the  other  hand,  if  one  admits 
that  Basedow  patients  are  not  surgical,  why  refer  them  to  the  surgeon 
at  all  ?  Why  not  bear  the  full  responsibility  of  the  decision  ?  So  long 
as  thyrotoxic  cases  shall  be  referred  to  the  surgeon  in  the  late  stage 
only  we  shall  have  the  sorrow  of  registering  only  incomplete,  unsatis- 
factory results,  while  the  death-rate  will  continue  to  be  high  and 
failures  numerous.  It  is  not  the  first  time  that  we  have  had  to  experience 
the  disheartening  lack  of  support  from  medical  men  in  some  of  our  big 
medical  problems,  as,  for  example,  in  the  field  of  appendicitis,  gastric, 
and  duodenal  ulcer,  etc.  In  such  fields  we  have  finally  won  out.  No 
one  today  would  think  of  treating  medically  a  case  of  appendicitis  unless 
for  some  special  reason.     Appendicitis  has  become  a  surgical  disease,  yet, 


SURGICAL   TREATMENT  OF  EXOPHTHALMIC  GOITER         431 

there  is  no  doubt  that  appendicitis  can  be  cured  medically  in  a  number 
of  cases.  Why  not  then  remain  consistently  true  to  this  latter  form  of 
treatment?  It  is  because  when  a  case  of  appendicitis  begins,  no  one 
knows  precisely  the  course  it  is  going  to  take;  how  and  when  it  is  going 
to  terminate;  whether  it  is  going  to  perforate,  to  cause  a  diffuse  peri- 
tonitis, or  a  fistula  with  one  of  the  intra-abdominal  organs,  or  a  thrombo- 
phlebitis, an  endocarditis,  nephritis,  hepatitis,  or  a  subphrenic  abscess, 
or  a  purulent  pleurisy,  etc.,  and  finally,  to  cause  death.  While,  on 
the  other  hand,  if  the  offending  appendix  is  removed  in  the  early  stage 
of  the  inflammatory  process,  all  these  complications  are  mostly  avoided, 
and  as  a  result  the  death-rate  is  reduced  to  the  minimum.  The  same 
is  true  for  thyrotoxicosis.  No  one  can  tell  what  an  incipient  case  of 
hyperthyroidism  is  going  to  do,  whether  or  not  it  is  going  to  transform 
itself  into  a  fulminating  or  a  more  chronic  form  of  thyrotoxicosis;  what 
the  extent  of  the  permanent  damage  to  the  organs  of  the  individual 
will  be;  how  many  rears  the  period  of  invalidity  is  going  to  take,  and  to 
what  extent  the  depreciation  of  the  individual  will  amount  to  at  last, 
while,  on  the  other  hand,  if  we  operate  in  the  true  incipient  stage,  we 
know  from  experience  that  we  shall  have  not  far  from  ioo  per  cent,  of 
permanent  cures  and  practically  no  deaths.  Why  should  we  hesitate 
then  ?  In  my  earliest  experience  I  had  a  number  of  times  the  sorrow  of 
seeing  patients,  to  whom  I  had  advised  a  course  of  medical  treatment 
for  their  incipient  hyperthyroidism,  come  back  later  in  a  pitiful  state. 
We  should  never  forget  that  Basedow  patients  are  fragile,  that  a  slight 
infection,  or  a  benign  operation  is  liable  to  cause  serious  accidents;  that 
the  more  the  disease  progresses,  the  more  chronic  changes  take  place  in 
the  organs,  and  consequently,  the  less  probable  are  the  chances  for 
success.  In  order  to  demonstrate  this  very  thing,  Schultze  went  over 
the  cases  operated  by  Riedl.  He  divided  the  cases  into  three  series,  the 
light,  the  medium,  and  the  severe  forms.  The  light  forms  gave  ioo 
per  cent,  of  cure;  the  medium  forms  6  per  cent,  death  and  two-thirds 
cure,  the  severe  forms  57  per  cent,  success  and  2S  per  cent,  death. 

Kocher,  Riedl,  Landstrom,  Mayo,  etc.,  all  consider  surgical  treatment 
as  the  safest,  surest,  best  and  most  satisfactory  way  of  handling  the  dis- 
ease. A  study  of  the  statistics  bears  out  their  statements.  It  is  only 
justice,  however,  to  say  that  some  of  the  best  medical  men  are  fast 
coming  to  recognize  the  necessity  of  surgical  treatment.  1  he  example 
comes  from  such  notable  medical  clinics  as  those  of  von  Noorden,  I  1. 
Miiller,  and  of  others,  where  the  eases  of  Graves'  disease  which  do  not 
respond  promptly  to  medical  treatment  are  advised  to  undergo  surgical 
treatment.  Barker,  one  of  our  eminent  American  internists,  said  that 
the  treatment  of  Graves'  disease  belongs  to  the  surgeon.  Lemke  said 
the  same  thing. 


432         SURGICAL  TREATMENT  OF  EXOPHTHALMIC  GOITER 

It  would  be  a  mistake,  however,  to  think  that  every  thyrotoxic  case 
should  be  operated.  Each  patient  is  a  problem  in  himself,  and  only 
experience  and  judgment  will  tell  what  is  the  proper  thing  to  be  done  in 
each  given  case.  One  thing  is  certain:  there  is  a  class  of  thyrotoxic 
patients,  which,  properly  handled,  can  be  cured  by  medical  means.  To 
operate  on  such  would  be  to  perform  unnecessary  operations.  On  the 
other  hand,  there  is  another  class  of  patients  which  are,  by  right,  abso- 
lutely surgical. 

It  is  often  said  that  any  thyrotoxic  case  which  has  been  under  medi- 
cal treatment  for  a  certain  period  of  time  and  that  does  not  show  any 
decided  improvement,  should  be  turned  over  to  the  surgeon.  This  is, 
of  course,  true,  but  it  may  sometimes  be  difficult  to  decide  when  medi- 
cal treatment  has  become  insufficient  and  when  the  psychological  time 
to  resort  to  surgical  treatment  has  come.  Some  authors  set  down  hard- 
and-rigid  rules  and  claim  that  if  a  patient  after  "six  weeks  or  three 
months"  of  medical  treatment  is  not  on  the  road  to  recovery,  he  should 
be  operated.  Although  this  is,  on  the  whole,  a  wise  rule,  mathematical 
rules,  however,  do  not  fit  this  disease  of  such  protean  and  deceiving 
character.  It  is  not  so  much  a  matter  of  time  as  it  is  a  matter 
of  judgment.  Indications  change  from  one  patient  to  another.  There 
are  cases  which  should  be  operated  at  once,  and  then  again  there  are 
other  cases  which  could  be  treated  medically  for  a  much  longer  period 
of  time  without  running  the  risk  of  impairing  the  chances  of  success, 
should  an  operation  eventually  have  to  be  resorted  to.  As  Moebius 
said,  "We  should  not  operate  too  soon,  nor  too  late." 

As  a  matter  of  fact,  we  are  practically  never  called  upon  to  operate 
in  cases  in  which  the  diagnosis  is  doubtful.  The  great  majority  of  cases 
have  been  diagnosed  over  and  over  again,  and  repeatedly  apparently 
cured,  so  that  actually  from  a  surgical  stand-point  the  result  does  not 
depend  so  much  upon  the  diagnosis  of  Graves'  disease  as  it  does  upon  the 
operable  condition  of  the  patient. 

When  once  an  operation  has  been  decided  upon,  the  judgment  and 
experience  of  the  surgeon  will  be  largely  the  determining  factors  for  the 
safe  outcome  of  the  case.  Surgeons,  because  they  have  done  too  much, 
have  killed  a  great  number  of  patients  with  exophthalmic  goiter;  also,  they 
have  killed  many  others  because  they  have  used  a  general  anesthetic 
when  they  should  have  used  a  local  one,  or  because  they  have  subjected 
their  patients  to  an  operation  near,  or  at  the  top  of  a  wave  of  hyperthy- 
roidism, or  because,  as  some  one  has  said,  "they  have  done  the  right 
thing  at  the  wrong  time,  or  the  wrong  thing  at  the  right  time."  There 
is  no  other  field  in  surgery  in  which  more  than  in  the  thyrotoxic  field, 
the  surgeon  must  be  first  and  above  all  a  good  diagnostician.  Here  he 
must  be  able  to  appreciate  the  strength  of  a  given  heart,  to  judge  how 


SURGICAL  TREAT M EXT  OF  EXOPHTHALMIC  GOITER         433 

much  shock  a  nervous  system  will  be  able  to  stand  and  how  much  it 
will  not;  to  know  whether  the  case  is  complicated  with  thymus  enlarge- 
ment or  not,  or  whether  the  degenerative  processes  in  the  organs  have 
gone  so  far  as  to  compromise  the  safety  of  the  operation.  Then  there 
comes  next  the  complete  mastery  of  the  surgical  technic,  as  the  other 
asset  for  success.  But  even  then,  with  the  best  medicosurgical  judg- 
ment and  experience,  every  surgeon  will  sometimes  meet  with  misfor- 
tune because  the  conditions  found  are  deceiving.  A  heart  seems  to 
respond  beautifully  to  a  preliminary  treatment  but  great  is  our  surprise 
to  find  that  when  this  heart  is  expected  to  stand  by  us,  it  simply  quits. 
Again,  in  another  case  the  wave  of  hyperthyroidism  seems  to  be  tided 
over;  and  surgical  interference  seems  to  be  safe,  vet,  an  acute  spell  of 
hyperthyroidism  follows  the  surgical  act  so  that  death  may  ensue.  Or 
in  still  another  case  the  operation  takes  place  just  when  an  acute  spell  of 
hyperthyroidism  is  in  its  latent  stage.  Here  the  operation  acts  as  an 
explosive  and  determines  a  very  acute  spell  of  hyperthyroidism.  Then, 
too,  there  are  unavoidable  casualties  due  to  pneumonia,  acidosis, 
nephritis,  etc. 

It  is  often  said  that  we  surgeons  "select"  our  cases.  If  by  this  is 
meant  that  we  refuse  our  help  whenever  there  is  a  risk,  simply  for  the 
sake  of  being  able  to  publish  beautiful  statistics,  then  it  is  not  true. 
We  all  operate  thyrotoxic  cases  whenever  there  is  a  chance  of  bringing 
about  a  cure  or  even  relief.  But,  if  it  is  meant  that  we  do  not  operate 
indiscriminately  all  the  exophthalmic  goiter  patients  without  giving 
their  condition  careful  attention  and  without  weighing  the  chances  for 
success,  then  the  assertion  is  very  true  and  to  our  credit.  I  will  say 
more,  it  is  our  duty  to  do  so.  It  is  only  by  weighing  carefully  all  the 
minute  pros  and  cons,  and  by  taking  into  consideration  what  Mayo 
calls  the  "factors  of  safety,"  that  men  like  Kocher,  Mayo,  and  many 
others  have  reduced  their  mortality  to  practically  nothing  and  have 
obtained  such  brilliant  results. 

\\  hen  men  like  Crile,  for  instance,  give  credit  for  their  improved 
results  and  diminished  death-rate  to  their  methods,  such  as  anoci- 
association  and  nitrous  oxide,  etc.,  I  feel  that  they  are  too  generous 
toward  their  methods  and  too  unjust  toward  themselves.  I  hey 
should  not  forget  that  in  the  course  of  years  their  medicosurgical 
judgment  has  improved,  and  that  experience  lias  taught  them  that 
in  Graves'  disease  there  is  a  danger-zone  which  no  one  darts  to 
pass  without  great  risks;  that  the  surgical  traumatism,  no  matter  how 
small,  must  be  graduated  to  the  resistance  of  the  patient,  that  there  are 
"factors  of  safety"  which  cannot  be  ignored  without  punishment.  1  hat 
this  must  be  SO  is  shown  by  the  fact  that  men  who  do  not  make-  it  a 
practice  of  applying  tin-  same  methods  such  as  anoci-association  and 

28 


434         SURGICAL  TREATMENT  OF  EXOPHTHALMIC  GOITER 

nitrous  oxide,  for  instance,  have  just  as  good  results,  to  say  the  least. 
Who  can  beat,  for  instance,  Kocher's  and  Mavo's  statistics  so  far  as 
results  are  concerned  ?  Yet  Kocher's  patients,  unless  physically  unfit, 
walk  from  their  bed  to  the  operating  room  where  surgical  preparation 
is  made  over  again;  they  undergo  the  operation  under  local  anesthesia, 
with  the  full  knowledge  that  the  operation  is  being  performed,  and  after 
the  operation,  as  a  rule,  walk  back  to  their  beds.  We  all  know  that  a 
painless  local  anesthesia  is  a  difficult  matter  to  obtain,  so  that  conse- 
quently the  elements,  pain  and  fear  are  not  absolutely  eliminated.  Yet 
his  death-rate  is  less  than  i  per  cent,  and  his  cures  between  75  and  80 
per  cent.,  while  the  rest  are  materially  improved.  Why  should  it  be  so 
if  the  whole  problem  should  resolve  itself  into  a  question  of  psychic  and 
painful  stimuli  ?  As  a  matter  of  fact,  the  whole  secret  lies  in  the  careful 
graduation  of  the  surgical  traumatism,  no  matter  if  ether,  nitrous  oxide, 
or  local  anesthesia  is  used;  it  lies,  too,  in  the  careful  selection  of  the  psy- 
chological time  for  the  surgical  venture.  All  the  other  conditions  are 
good  adjuvants,  but  not  essential. 

What  Line  of  Conduct  Shall  We  Follow  in  Deciding  the  Course  of  Treat- 
ment for  Each  Given  Case? — The  following  is  the  one  which  has  served 
the  writer  as  a  guide: 

1.  A  secondary  or  Basedozvified  goiter,  whether  causing  mechanical 
symptoms  or  not,  is  by  right  surgical.  Here  thyrotoxicosis  is  secondary 
to  the  presence  of  that  goiter,  be  it  colloid  or  cystic,  or  malignant,  and 
as  soon  as  the  goiter  is  removed  thyrotoxicosis  subsides.  These  cases 
are  the  ones  in  which  the  results  are  among  the  most  gratifying.  They 
respond  quickly  to  the  surgical  treatment,  and  provided  the)*  are  not 
too  bad  surgical  risks,  the  death-rate  is  low. 

2.  The  early  mild  forms  of  hyperthyroidism  in  young  individuals 
should  be  treated  medically.  We  often  see  young  women  in  schools  and 
colleges,  girls  and  debutantes  react  to  overwork  and  undue  excitement 
with  a  mild  form  of  hyperthyroidism.  They  complain  of  nervousness, 
palpitation,  insomnia,  loss  of  appetite,  muscular  asthenia;  the  cardiac 
action  runs  up  to  100  or  higher;  they  have  a  moderate  thyroid  hyper- 
plasia. This  class  of  patients  should  be  the  triumph  of  medical  treat- 
ment. Such  patients  should  be  treated  with  rest  in  bed  for  several 
weeks  or  months  until  the  condition  has  subsided.  Furthermore,  their 
activities  should  be  stopped  and  complete  relaxation  obtained.  Here 
all  physical  as  well  as  medicinal  means  which  medical  treatment  pos- 
sesses can  be  applied.  Even  a  few  carefully  applied  .%-ray  treatments 
might  prove  of  value  in  stopping  thyrotoxicosis  in  its  embryonic  stage. 
If,  however,  despite  a  medical  treatment  intelligently  applied,  the  condi- 
tion shows  a  progressive  tendency  an  early  operation  should  be  resorted 
to  in  order  to  bring  about  a  cure.  The  results  are  certain,  almost  ico 
per  cent.,  and  the  death-rate  practically  negative. 


COURSE  OF  TREATMENT  FOR  EACH  GIVEN  CASE  435 

3.  The  early  typical  cases  are  surgical  cases.  Just  as  in  acute  appen- 
dicitis, we  do  not  wait  for  perforation  and  general  peritonitis  to  take 
place,  so  in  these  cases  we  should  not  wait  until  the  condition  has 
become  too  severe  before  interfering  surgically.  If  the  patient  seeks 
medical  aid  for  the  first  time  and  medical  treatment  has  not  been  applied, 
it  is  well  to  give  it  a  short  but  fair  trial  with  the  view  of  preparing  the 
patient  for  an  operation.  If  in  the  meantime  the  condition  subsides 
quickly,  all  well  and  good.  If  not,  or  if  when  cured,  these  cases  show  a 
tendency  to  relapse,  then  operation  should  be  resorted  to  without  much 
delay.  This  is,  too,  a  class  of  patients  where  surgery  can  boast  of  not 
far  from  100  per  cent,  cure  and  a  low  mortality. 

In  this  class  of  cases  the  social  condition  of  the  patient  has  an  impor- 
tant bearing  upon  the  decision  to  be  taken.  If  the  patient  belongs  to 
the  more  fortunate  class,  who  therefore  can  devote  time  and  money 
to  recuperation,  and  can  go  from  one  resort  to  another,  the  medical 
treatment  may  be  given  a  longer  trial,  provided  the  disease  loses  its 
progressive  character.  But  unfortunately  a  great  number  of  these 
patients  do  not  belong  to  this  favored  class.  Either  they  must  make 
their  own  living,  or  they  have  large  families  to  take  care  of,  or  they  have 
to  live  on  what  they  have  saved.  It  is  consequently  impossible  for 
them  to  undergo  an  adequate  course  of  treatment  with  the  necessarv 
physical  and  mental  rest  and  perhaps  change  of  environment  before 
and  after  treatment.  In  such  cases  it  would  be  unreasonable  to  ask 
such  patients  to  devote  months  and  years  to  rest  cure  and  medicinal 
treatment.  The  best  and  only  treatment  for  this  class  of  patients  is  an 
early  operation.  But  do  not  think  for  one  moment  that  wealth  will 
protect  rich  patients  and  save  them  from  surgical  treatment.  If  they 
belong  to  the  rich  class  they  do  not  necessarily  belong  to  the  privileged 
class,  so  far  as  health  is  concerned.  Indeed  I  am  safe  in  saying  that  in 
Graves'  disease  the  wealthy  furnish  a  heavy  contingent  of  such  patients. 

4.  In  the  well-advanced  typical  cases  no  time  should  be  lost  before 
an  operation,  whatever  it  may  be,  is  performed.  Such  cases,  as  a  rule, 
have  already  run  the  gamut  of  medical  means;  they  have-  had,  off  and 
on,  periods  of  welfare  alternating  with  periods  of  exacerbation;  they  have 
very  likely  been  discharged  as  medically  cured  more-  than  once-,  and 
each  relapse-  has  left  them  just  a  little-  more-  vulnerable  than  before. 
Not  only  have  such  cases  long  since  passed  the  medical  stage-,  but  they 
are-  also  no  longer  safely  surgical.  I  he  immediate  family  should  be  told 
frankly  that  a  complete  recovery  is  possibly  no  longer  to  be  hoped  for, 
and  that  in  that  stage  the-  death-rate  is  higher. 

5.  The  severe  advanced  cases  of  long  standing  have,  so  to  speak, 
passed  the  surgical  stage;  they  have  become-  damaged  beyond  the  possi- 
bility ot  repair;  the}  have  become  medical  again.  Indeed,  in  such  cases 
the  organic  changes  in  the  various  organs  of  the  bod\   such  as  the  heart, 


436         SURGICAL   TREATMENT  OF  EXOPHTHALMIC  GOITER 

liver,  kidneys,  etc.,  have  become  so  marked  that  hope  of  a  cure  is  out 
of  the  question.  Their  whole  organism  is  so  completely  disorganized, 
and  their  resistance  so  impaired,  that  an  operation  as  light  as  it  may  be 
is  not  a  procedure  to  go  into  without  considerable  prudence.  In  such 
cases  if  there  are  reasonable  chances  for  safety  for  surgical  treatment 
a  ligation  might  be  made.  When  once  such  patients  have  withstood 
the  surgical  shock  it  is  sometimes  remarkable  to  see  how  much  such  a 
light  operation  will  improve  their  condition.  It  will  often  put  them  into 
such  a  favorable  condition  that  later  on  they  will  be  able  to  stand  further 
surgical  procedures.  We  all  in  our  experience  have  seen  similar  cases 
which  have  been,  so  to  speak,  grabbed  out  of  the  grave  and  restored  to 
a  life  of  comparative  comfort.  But  unfortunately  it  is  this  class,  too, 
which  furnishes  the  highest  mortality.  If,  for  safety's  sake,  any  surgical 
procedure  is  forbidden,  x-rays  or  boiling-water  injections  may  afford 
some  relief,  although  the  prospect  for  this  is  not  very  great;  these  thy- 
roids have  been  already  "burned  out"  by  the  thyrotoxic   fire   (Fig.  69). 

6.  The  fulminating  forms  of  Graves'  disease  present  roughly  three 
types:  the  cardiovascular,  the  gastro-intestinal,  and  the  asthenic  type, 
the  latter  resembling  largely  the  profound  physical  prostration  of  Addi- 
son's disease.  Theoretically,  these  fulminating  forms  should  be  from  the 
start  surgical;  practically,  however,  most  of  them  can  be  only  medical. 
Indeed,  in  such  cases  the  symptoms  of  intoxication  are  so  intense  and 
the  progress  of  the  disease  so  rapid,  that  there  is  scarcely  any  time, 
except  in  the  early  beginning,  for  surgical  procedure.  To  operate  when 
the  wave  of  hyperthyroidism  is  at  its  highest,  when  the  gastro-intestinal 
symptoms  are  at  their  worst,  when  tachycardia  is  in  the  neighborhood 
of  200  and  possibly  more,  would  be  to  expose  the  patient  to  a  more  or 
less  certain  death.  In  this  class  of  cases  anything  which  is  known  to  be 
of  value  in  medicosurgical  therapeutics  must  be  attempted  and  that 
quickly.  According  to  Beebe  it  is  in  these  fulminating  forms  that  serum 
treatment  has  shown  its  most  striking  results;  and  according  to  him 
the  relief  obtained  in  such  cases  is  quite  as  striking  as  that  obtained  in 
diphtheria  through  the  administration  of  antitoxin.  If,  perchance, 
during  the  rapid  progress  of  the  condition,  there  should  occur  a  period 
of  subsidence,  a  ligation  may  under  local  anesthesia  be  attempted.  In 
the  meantime,  the  x-rays  and  boiling-water  injections  may  prove  a  very 
efficient  means  to  tide  the  patient  over  the  dangerous  period.  When 
that  is  done,  no  time  should  be  lost  in  performing  whatever  surgical 
interference  is  deemed  safe  and  necessary. 

7.  As  a  general  principle,  any  thyrotoxic  case  which  shows  a  tendency 
to  become  chronic  or  to  relapse  should  be  operated.  When  a  case  has 
gone  through  an  acute  spell  of  hyperthyroidism  and  has  subsided,  the 
"interval  operation"  is  the  safest  procedure. 


COURSE  OF  TREAT M EXT  FOR  EACH  GIVEX  CASE  437 

8.  The  fruste  forms  of  hyperthyroidism  are  nearly  all  medical.  The 
patients  of  this  group  often  show  the  most  bizarre  combination  of  hypo- 
thyroidism, hyperthyroidism,  and  of  polyglandular  symptoms.  Conse- 
quently careful  analysis  of  the  syndrome  should  be  made  in  order  to 
derive  a  rational  medical  treatment.  Only  when  medical  means  prop- 
erly and  intelligently  applied  for  a  sufficiently  long  period  of  time  have 
failed  to  bring  about  the  necessary  relief,  can  one  then  resort  to  opera- 
tion. In  this  class  of  cases  the  results  obtained  from  operation  are  slow 
to  show  up.     On  the  whole  the)*  are  unsatisfactory  to  treat. 

9.  An  acute  exacerbation  is  an  absolute  contra-indication  to  opera- 
tion, no  matter  at  what  stage  the  case  may  be.  It  is  necessary  to  wait 
until  this  spell  has  subsided. 

10.  A  patient  with  a  weak  and  dilated  heart,  as  shown  by  the  Kat- 
zenstein  test,  or  one  with  a  low  blood-pressure,  is  one  in  whom  the  dan- 
gers of  any  surgical  treatment  are  greatly  increased.  This  class  of  cases 
should  be  treated  medically  until  an  operation  can  be  deemed  safe.  If, 
however,  the  case  grows  steadily  worse,  it  then  becomes  an  emergency 
one  in  which  something  must  be  done.  In  that  case  the  surgical  trauma- 
tism must  be  graduated  to  the  patient's  condition. 

11.  A  certain  degree  of  myocarditis,  or  of  valvular  lesions,  provided 
they  are  well  compensated,  or  a  moderate  amount  of  glycosuria,  is  no 
absolute  contra-indication  to  operation. 

12.  The  presence  of  a  thymic  hyperplasia  is  by  no  means  a  contra- 
indication for  operative  treatment,  but  rather  a  strong  indication  in  its 
favor.  In  my  practice  thymectomy  is  performed  as  a  routine  procedure 
in  every  goiter  operation  whenever  thymic  hyperplasia  is  present. 

13.  Should  a  patient  who  has  been  operated  on  not  improve  in  the 
manner  in  which  he  is  expected  to,  or,  after  a  period  of  welfare,  should 
he  relapse,  this  does  not  indicate  a  failure  of  the  surgical  principle.  If  a 
medical  case  does  not  improve  sufficiently,  or  relapses  after  a  period  of 
improvement,  the  treatment  is  renewed  with  more  energy.  The  same  is 
true  for  surgical  treatment.  A  number  of  these  cases  belong  to  that 
class  of  patients  which  Kocher  considers  as  "nicht  fertig  openert." 

14.  As  a  general  principle,  in  exophthalmic  goiter  surgery,  it  is  better 
to  err  in  favor  of  conservatism,  and  when  in  doubt,  it  is  by  far  safer  to 
ligate  instead  of  to  thyroidectomize,  and  to  resort  to  two  ligations  instead 
of  three,  one  instead  of  two.  It  is  better  to  have  an  imperfect  result 
than  it  is  to  have  death,  inasmuch  as  the  first  alternative  may  In- 
remedied  by  a  subsequent  operation,  whereas  the  latter  is  beyond 
one's  reach. 

15.  When  once  a  patient  has  been  opt  rated  on,  he  becomes  again  a 
medical  patient.  He  should  be  followed  medically  until  cure  is  assured. 
The  same  medical   principles  which   apply   prior  to  the  operation   rind 


438         SURGICAL  TREATMENT  OF  EXOPHTHALMIC  GOITER 

their  indication  and  usefulness  after  the  operation:  rest,  change  of  envi- 
ronment, automobihng,  sojourn  in  mountainous  regions,  are  the  best 
adjuvants  of  the  surgical  treatment. 

As  seen  bv  this  outline,  Graves'  disease  is  a  medico  surgical  disease, 
and  one  in  which  both  the  physician  and  surgeon  must  have  something 
to  say.  The  physician  prepares  the  road  for  the  surgeon  and  when  the 
work  is  done,  gives  it  its  finishing  touch.  Great  things  today  are  not 
done  bv  the  individual  alone,  but  by  cooperative  work.  There  is  no 
other  field  in  medicine  where  the  "team-work"  principle  can  be  applied 
to  better  advantage.  We  often  hear  some  internists  ridicule  the  fact 
that  surgeons  require  their  patients  to  follow  a  course  of  medical  treat- 
ment after  their  operations.  Why,  that  is  the  most  logical  thing  to  do! 
Indeed,  since  the  systemic  disturbances  are  often  very  marked,  although 
the  primary  cause,  namely,  the  thyroid  has  been  removed,  it  will  never- 
theless, take  quite  a  long  time  before  the  organism  finds  its  normal 
equilibrium  again.  The  entire  complicated  machinery  of  the  organism 
must  readjust  itself.  No  one  will  think  of  feeling  shocked  because  gastro- 
enterostomy for  gastric  ulcer,  gastric  resection  for  cancer,  will  require  a 
postoperative  medical  assistance  for  quite  a  long  time.  Why,  then,  feel 
scandalized,  for  exactly  the  same  thing  in  thyroid  surgery  ?  Let  it  be 
said  that  petty  disputes  will  not  advance  the  matter  any,  and,  be  it 
as  it  may,  if  it  is  to  the  better  advantage  of  the  patients  to  so  treat  them, 
let  us  do  so. 

Medical  men,  says  Halstead,  have  every  right,  if  they  so  choose,  to  try 
non-surgical  measures  in  the  early  stages  of  the  disease.  But  if,  failing  not 
only  to  arrest  the  disease  but  also  to  cure  their  patients  quickly,  they  do 
not  advise  operation  in  the  safe  and  curable  stage,  they  should  be  held  to 
as  strict  accountability  as  when  they  fail  to  call  for  surgical  help  until  a 
patient  with  acute  appendicitis,  for  example,  has  developed  a  general 
diffuse  peritonitis.  Let  us  recall  the  words  of  our  great  master,  Kocher, 
when  he  said,  speaking  to  the  internists,  ''Gentlemen,  do  not  fail  to 
send  us  your  patients  early.  We  will  send  them  back  to  you  and  in  so 
doing  will  find  in  our  work  better  results  and  more  pleasure." 


CHAPTER   XL. 

SURGICAL  TECHNIC  OF  OPERATIONS   UPON  THE 
THYROID  GLAND. 

Surgical  technic  in  goiter  operations  has  improved  enormously  in 
the  last  fifteen  years.  These  results  are  especially  due  to  Kocher  and 
his  school,  to  the  German  school,  of  whose  members  W olfler,  Billroth, 
Mikulicz,  von  Eiselsberg,  and  a  few  others  rank  first;  to  the  French 
school,  especially  that  of  Lyon  counting  Poncet,  Berard,  Delore  and  Ala- 
martine  among  its  first  members.  In  America,  Charles  H.  Mayo,  Ochsner, 
Halstead,  etc.,  have  done  their  share  toward  generalizing  and  improving 
thyroid  surgery. 

A  uniform  technic  does  not  exist.  Every  surgeon  puts  into  his  work 
the  seal  of  his  own  individuality,  consequently  divergence  of  details 
will  always  be  found;  fundamental  differences,  however,  do  not  exist  any 
longer. 

Good  surgery  must  always  be  based  upon  the  exact  knowledge  of 
the  anatomy,  physiology,  and  pathology  of  the  organ  against  which  it 
is  directed.  It  must  take  into  consideration,  too,  certain  desiderata  and 
certain  principles  which  must  be  aimed  at  if  one  wishes  to  obtain  the 
maximum  of  results  from  the  operation.  Fifteen  to  twenty  years  ago 
the  main  thing  was  to  have  the  goiter  out,  no  matter  how  or  at  what 
cost.  To  be  sure,  the  scar  was  not  always  very  pretty,  while  the  inferior 
laryngeal  nerve  did  not  always  escape  injury,  and  a  slight  touch  of 
tetany  was  not  to  be  wondered  at.  Then,  too,  some  hypothyroidism 
was  only  too  natural  and  lucky  it  was  if  it  did  not  develop  into  a  hill 
myxedema!  Today  these  views  are  no  longer  acceptable.  Our  knowl- 
edge of  the  condition  has  advanced;  our  technic  has  become  more  pre- 
cise, and  then,  too,  the  public  has  become  more  critical.  Consequent^ 
before  LL<>mg  into  the  description  of  the  operation  itself  let  ns  go  over 
the  anatomical  and  pathological  conditions  in  which  an  operation  takes 
place-;  let  us  decide  what  is  anatomically  important  and  what  can  be 
left  out;  let  us  discuss,  too,  these  different  requirements  which  give  to 
the  technic  its  present  characteristics. 

Before  going  any  further  lei  us  ;isk: 

\\  hat  are  these  desiderata  : 

\\  c  w  ant  : 

i.  To  have  constantly  present  in  our  minds  a  few  particular  anatomi- 
cal tacts  from  which  will  derive  certain  important  technical  procedures. 


440      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

2.  To  leave  the  parathyroids  and  the  inferior  laryngeal  nerve 
uninjured. 

3.  To  leave  enough  thyroid  tissue  so  as  to  protect  the  patient  against 
future  hypothyroidism. 

4.  To  protect  the  patient  against  future  relapses. 

5.  As  fine  and  as  nearly  invisible  a  scar  as  is  possible. 

6.  To  shape  the  neck  so  as  to  render  it  esthetic. 

Anatomical  Facts. — Surgery  of  the  thyroid  became  simple  the  day 
the  surgeons  learned  to  utilize  the  normal  and  pathological  intra-  as 
well  as  perithyroidal  planes  of  cleavage. 

Let  us  suppose  that  we  make  a  transverse  incision  in  the  thyroid 
region  of  the  neck,  and  retract  the  upper  and  lower  cutaneous  flaps  in 
their  respective  directions,  we  shall  then  find: 

1.  The  sternocleidomastoid  muscles  and  the  prethyroidal  muscles 
which  are  the  sternohyoid,  omohyoid,  and  underneath,  the  sterno- 
thyroid muscles.  These  muscles  are  covered  by  the  superficial  cervical 
fascia.  Starting  from  the  ligamentum  nuchae  this  fascia  forms  a  sheath 
for  the  trapezius  muscle,  passes  over  the  entire  posterior  triangle  of  the 
neck  until  it  reaches  the  posterior  border  of  the  sternocleidomastoid 
muscles.  There  it  forms  a  sheath  for  this  muscle,  passes  over  the 
anterior  triangle  of  the  neck,  and  finally  meets  in  the  middle  line  the 
superficial  cervical  fascia  from  the  other  side. 

2.  Extending  from  one  omohyoid  muscle  to  the  other,  and  from  the 
hyoid  bone  to  the  manubrium  sterni  and  to  the  middle  of  the  clavicles, 
the  middle  cervical  fascia  forms  a  sheath  for  the  three  thyroidal  muscles, 
goes  toward  the  middle  line  and  there  fuses  with  the  one  of  the  other 
side  and  the  superficial  cervical  fascia,  thus  forming  the  cervical  linea 
alba. 

3.  The  middle  cervical  fascia  and  the  prevertebral  fascia  give  origin 
to  a  loose  connective-tissue  capsule  which  surrounds  the  thyroid  gland 
and  is  easily  detachable.  Let  us  call  that  capsule  the  surgical  capsule 
of  the  thyroid.      (Plate  IX,  Fig.  1.) 

4.  The  thyroid  parenchyma  is  surrounded  by  a  capsule  which  is  the 
equivalent  of  the  one  seen  in  other  glandular  organs  such  as  the  capsule 
of  Glisson  for  the  liver,  the  albuginea  for  the  testicle,  the  renal  capsule 
for  the  kidneys,  etc.  It  is  in  close  relation  with  the  parenchyma  and 
sends  inwardly  septa  dividing  the  parenchyma  into  lobi  and  lobuli  and 
finally  surrounds  each  alveoli  with  a  very  thin  layer  of  connective  tissue, 
the  glandular  capsule.      (Plate  IX,  Fig.  1.) 

5.  Between  the  sternocleidomastoid  muscles  and  the  prethyroid 
muscles  there  is  a  normal  plane  of  cleavage.  De  Quervain  calls  it  the 
sternomastoid  space.     (Plate  IX,  Fig.  1.) 

6.  Between  the  prethyroid  muscles  and  the  surgical  capsule  there  is 
another  plane  of  cleavage,  the  musculocapsular  space.     (Plate  IX,  Fig.  1.) 


-■^i^totx/f 


"    s    istind 


Cross-section  of  the  Neck  with  its  Various  Organs,  Showing 
the  Relation  of  the  Thyroid  to  the  Neighboring  Tissues  and  the 
Various  Spaces  Described  in  the  Text. 


Danger  Zone. 

The  relation  of  the  carotid  sheath,  inferior  laryngeal  nerve,  inferior  thyroid  artery, 
middle  vein,  parathyroids,  and  of  the  posterior  surface  of  the  thyroid  gland  to  each 
othei.  The  dotted  curved  line  shows  where  resection  should  take  place  in  order  to 
avoid  injury  to  these  various  organs. 


ANATOMICAL  FACTS 


441 


7.  Finally,  between  the  glandular  capsule  and  the  surgical  capsule 
there  is  another  plane  of  cleavage  formed  of  loose  connective  tissue  and 
containing  numerous  arteries  and  veins,  the  intercapsular  or  surgical 
space.  (Plate  IX,  Fig.  1.)  It  surrounds  the  thyroid  gland  entirely  and 
extends  from  one  side  of  the  trachea  and  the  esophagus  to  the  other  side. 

The  relations  between  the  glandular  capsule  and  the  surgical  capsule 
are,  as  a  rule,  very  loose.  It  is  only  on  the  postero-internal  surface  of 
the  thyroid  that  they  come  into  a  more  intimate  contact;  between  them 
a  great  number  of  arterial  and  venous  branches  are  found  going  in  and 
out  through  the  glandular  capsule.  Inwardly,  since  the  thyroid  is  inti- 
mately adherent  to  the  trachea,  no  plane  of  cleavage  may  be  expected 
to  be  found  there.  In  the  posterior  portion  of  this  perithyroid  cellular 
space  we  find  the  parathyroids  and  the  inferior  laryngeal  nerves.  Conse- 
quently we  must  regard  the  posterior  portion  of  this  perithyroid  cellular 
space  as  the  danger  zone  which  the  surgeon  must  carefully  avoid  during 
operation.      (Plate  IX,  Fig.  2.) 


Fig.  71. — Showing  proper  plane  of  cleavage  which  must  be  entered  into  before 
attempting  resection  of  the  thyroid.  Showing,  too,  how  much  thyroid  tissue  should  be 
left  in  contact  with  the  danger  /one  in  order  to  avoid  accidents.  I  he  intercapsular 
space  is  the  same  as  the  surgical  space. 

Such  are  the  anatomical  facts  grossly  described.  It  is  obvious  that 
the  musculocapsular  and  the  surgical  spaces  are  the  most  important  so 
far  as  the  surgical  technic  is  concerned.  The  surgical  space  is  the  "good 
plane  of  cleavage"  Fig.  71 )  which  must  be-  looked  for  if  the  surgeon  wishes 
to  make  an  easy  and  brilliant  thyroidectomy.  Die  surgical  capsule 
must  have  been  opened  and  the  surgical  space  found  before  attempting 
to  dislocate  the  goiter.  On  the  other  hand,  its  postero-internal  region 
must  be  absolutely   avoided   unless  one  wishes   to  expose   tin-  patient    to 


442      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

tetany  by  injuring  the  parathyroids,  or  to  vocal  disturbances  by  injur- 
ing the  inferior  laryngeal  nerves.  For  the  same  reasons,  it  follows,  too, 
that  when  resection  of  the  thyroid  is  being  performed,  one  should  pur- 
posely avoid  retracting  the  surgical  capsule  over  its  entire  course:  such 
retraction  should  take  place  only  just  enough  to  allow  manipulations 
on  the  thyroid  to  take  place  easily.  It  follows,  furthermore,  that  in 
order  to  avoid  injury  to  the  parathyroids  and  inferior  laryngeal  nerves, 
the  danger  zone  must  be  left  undisturbed.  (Plate  IX,  Fig.  2.)  This  is 
best  obtained  by  leaving  a  layer  of  glandular  tissue  in  contact  with  it 
while  resection  is  being   made. 

The  following  fact  is  interesting:  the  carotid  sheath  is  entirely  inde- 
pendent of  the  spaces  above  described,  for  it  possesses  a  space  of  its 
own:  the  carotid  space.  This  was  demonstrated  by  De  Quervain  by 
injecting  the  sheath  of  the  vascular  cord  at  the  angle  of  the  jaw  with 
gelatin.  The  gelatin  followed  the  vascular  cord  over  its  entire  course, 
filled  it  up,  but  did  not  fuse  in  any  way  with  the  one  of  the  ether  planes 
above  mentioned.  The  inferior  thyroid  artery  passes  behind  the  car- 
otid space  but  does  not  penetrate  into  it.  This  is  of  great  importance 
for  the  ligation  of  the  inferior  thyroid  artery,  as  the  carotid  sheath  can 
be  strongly  retracted  without  exposing  the  inferior  thyroid  artery  to 
injury. 

Pathological  Planes  of  Cleavage. — So  much  for  the  normal  planes  of 
cleavage.  The  pathological  ones  are  very  important,  too,  and  should 
be  known.  They  are  found  mostly  in  nodular  goiters,  cystic  or  colloid, 
and  must  be  always  taken  into  consideration  when  one  wishes  to  per- 
form an  enucleation.  In  nodular  goiters  the  pathological  plane  of 
cleavage  is  intraglandular  and  lies  all  around  the  nodule.  It  is  formed 
by  the  thickened  enveloping  membrane  of  the  nodule  itself,  and  by  a 
connective-tissue  formation  all  around  it  due  to  the  chronic  pressure  of 
the  nodule  on  the  parenchyma.  Between  these  two  layers  of  tissue  lies 
the  proper  plane  of  cleavage.  (Figs.  72  and  75.)  As  soon  as  it  is  found 
enucleation  takes  place  easily.  If  the  nodule  lies  at  the  periphery  of  the 
lobe  and  comes  in  contact  with  the  glandular  capsule,  the  latter  capsule 
may  fuse  together  with  the  nodule  so  as  to  destroy  entirely  at  that  point 
the  plane  of  cleavage.  This  plane,  however,  can  be  easily  found  by 
making  an  incision  in  the  neighboring  parenchyma  and  going  through 
it  until  the  nodule  is  reached. 

Blood  Supply  of  the  Thyroid. — It  had  been  thought  for  a  long  time 
that  the  thyroid  arteries  were  terminal.  These  conclusions  were  based 
mostly  on  the  researches  of  Hyrtl,  Anna  Begoune,  Jaeger-Luroth,  etc. 
Other  anatomists,  however,  as  Sappey,  Cruveilhier,  Thane,  etc.,  objected 
to  these  conclusions.  From  a  practical  stand-point  it  was  important  to 
settle  this  question  one  way  or  another:  indeed,  if  the  thyroid  arteries 


BLOOD  SUPPLY  OF  THE   THYROID  443 

were  terminal,  ligation  of  one  of  them  would  expose  the  territory  of  the 
gland  supplied  by  this  artery  to  necrosis.  On  the  other  hand,  if  thev 
anastomose  freely,  ligation  of  one  of  them  would  not  have  any  material 
effect  upon  the  intraglandular  circulation;  this  is  especially  important  in 
exophthalmic  goiter  work.  Lately,  Landstrom,  Delore,  and  Alamartine, 
have  reviewed  this  question.  The  writer  has  done  some  research  work 
in  that  line  by  injecting  through  one  or  more  of  the  thyroid  arteries  a 
20  per  cent,  benzin  solution  of  vermilion  and  controlling  the  results  with 
.\--rays.  The  following  conclusions  may  be  drawn:  the  superior  and 
inferior  thyroid  arteries  anastomose  freely  by  an  intricate  mingling  of 
their  terminal  branches  and  by  several  longitudinal  anastomoses:  the 
most  constant  and  most  important  one  of  them  follows  its  course  in  the 
tracheo-esophageal  angle.  (Plate  X,  Fig.  1.)  Bilateral  transverse 
anastomoses  exist,  too,  between  each  lobe.  Thev  are  less  numerous  and 
van'  greatly  in  volume,  and  they  connect  mostly  the  two  superior  thy- 
roid arterial  systems.  The  most  important  of  them  is  the  cricothyroid 
branch  which  lies  just  above  the  upper  border  of  the  isthmus  and  con- 
nects the  anterior  branches  of  the  superior  thyroid  artery.  This  com- 
municating branch  is  the  one  which  is  severed  when  performing  the 
cricothyroid  tracheotomy.  \  ery  often  there  is  another  transverse 
anastomosis  a  little  higher  up,  crossing  transversely  in  front  of  the  crico- 
thyroid membrane  and  connecting  the  two  superior  thyroid  systems. 
Besides  these  two  important  bilateral  anastomoses  there  are  many 
smaller  ones  connecting  the  branches  of  the  two  superior  arteries,  of  the 
posterior  longitudinal  anastomosis  and  of  the  cricothyroid  arteries:  they 
form  a  very  intricate  and  most  variable  arterial  plexus. 
r.  t-The  two  inferior  thyroid  arteries  communicate  with  each  other,  as  a 
rule,  through  anastomoses  connecting  the  longitudinal  anastomosis  of 
each  side.  However  numerous  these  anastomoses  are,  it  would  be  an 
error  to  believe  that  they  would  be  able  to  take  up,  off-hand,  the  blood 
supply  of  the  territory  whose  feeding  artery  has  been  severed.  To  a 
certain  extent  this  is  true  for  the  arteries  of  the  same  side,  for  the 
superior  artery  supplies  very  rapidly  and  abundantly  the  territory  of 
the  inferior  thyroid  when  the  latter  one  has  been  ligated,  and  vice  versay 
intraglandular  anastomoses  being  very  abundant  and  verj  effective.  It 
is  no  longer  quite  so  true  for  the  interlobar  anastomosis:  these  are  less 
abundant  and  less  effective.  I  here  really  exists  between  the  two  lobes 
a  certain  vascular  independence,  although  not  complete.  l)e  (Jucrvam 
very  judiciously  remarks  that  we  already  knew  clinically  what  these 
researches  brought  to  us.  Indeed,  it  alter  ligation  of  the  superior  and 
interior  thyroid  arteries  of  one  side,  resection  of  the  lobe  is  undertaken, 
one  can  see  plainly  that  the  arterial  hemorrhage  is  still  going  on,  though 
much  diminished.     1  think  even    surgeon  can  vouch  for  that. 


444      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

Besides  its  own  vascularization  the  thyroid  gland  possesses  another 
vascular  supply  coming  from  the  neighboring  tissues,  especially  the 
trachea  and  esophagus.  Landstrom,  Delore,  and  Alamartine  finally 
found  a  diffuse  system  of  anastomoses  connecting  the  superior  arteries 
with  the  prethyroid  muscles  and  subcutaneous  tissues.  This  entire  col- 
lateral supply  is  quite  important  and  is  sufficient  to  prevent  necrosis  of 
the  thyroid  after  ligation  of  the  four  thyroid  arteries. 

In  conclusion  we  may  say  that  the  thyroid  arteries  are  not  terminal. 
One,  two,  three,  even  all  four  thyroid  arteries  can  be  ligated  without 
exposing  the  gland  to  necrosis:  sufficient  vascular  supply  takes  place 
through  the  collateral  anastomosis  from  the  neighboring  organs,  even  if 
the  ima  artery  should  not  be  present. 

Which  one  of  the  thyroid  arteries  is  the  more  important,  the  superior 
or  the  inferior?  The  opinions  are  divided.  Von  Eiselsberg  and  the 
majority  of  German  authors  consider  the  inferior  thyroid  as  the  main 
one,  the  superior  being  only  a  secondary  artery.  De  Quervain  regards 
the  inferior  thyroid  artery  as  the  one  which  is  the  more  important.  The 
same  does  Halstead.  He  believes  that  the  inferior  thyroid  is  usually 
larger  than  the  superior  vessel  which  is  subject  to  greater  changes 
because  of  the  inconstant  position  of  the  superior  pole.  Delore  and 
Alamartine  do  not  share  the  same  view.  They  believe  that  the  superior 
thyroid  artery  is  the  more  important. 

In  the  superior  vertebrates  it  is  the  one  most  constantly  found, 
whereas  the  inferior  thyroid  is  not.  The  superior  thyroid  is  more 
constant  in  its  caliber,  in  its  mode  of  division,  and  in  its  course.  Its 
branches  of  division  cap  the  superior  pole.  The  superior  thyroid  artery 
follows  the  upper  pole  in  all  its  changes,  be  it  changes  in  form  or  posi- 
tion: where  the  upper  pole  is,  there  the  superior  thyroid  will  also  be 
found.  The  upper  pole  is  the  best  landmark  for  the  position  of  the 
superior  thyroid,  and  the  upper  pole  is  always  easily  found.  The  inferior 
thyroid,  on  the  other  hand,  is  much  more  variable  in  its  position  and 
volume.  It  does  not  cap  the  inferior  pole  as  does  the  superior  thyroid 
for  the  upper  pole,  but  passing  behind  the  vascular  cord,  approaches  the 
gland  laterally  at  the  junction  of  the  lower  with  the  two  upper  thirds, 
goes,  more  or  less,  far  behind  the  posterior  surface  and  only  then  pene- 
trates the  thyroid  gland.  (Plate  X,  Fig.  2.)  Like  the  superior  thyroid, 
it  follows,  too,  the  thyroid  gland  in  its  changes  of  form  and  position.  If 
the  inferior  pole  becomes  greatly  enlarged,  the  inferior  thyroid  artery 
becomes  somewhat  displaced,  but  never  to  such  an  extent  as  to  become 
intrathoracic,  for  instance.  Furthermore,  the  inferior  thyroid  artery 
divides  into  several  branches,  sometimes  very  far  from  its  point  of 
entrance  into  the  thyroid  gland,  so  that  it  is  not  uncommon  to  see  a 
surgeon  ligate  one  of  these  branches,  thinking  that  he  is  dealing  with 


w       ^  . 

Intracapsular  Resection. 

Showing  the  thin  capsule  which  remains  after  decortication  of  the  thyroid,  also 
how  easy  it  would  be  to  injure  the  parathyroids  and  infeiior  laryngeal  nerve.  These 
organs  are  seen  by  transparence  through  the  thin  capsular  veil.  Note,  too,  the 
longitudinal  anastomosis  between  the  superior  and  inferior  thyroid  arteries. 

FIG.    2 


-f>y  »t/ia//i,fi'r    y<i  ■ 


Normal   Anatomy  of  the   Deep  Cervical  Organs  Showing 
Their  Interrelation. 

The  relation  of  the  inferior  thyroid  to  the  sympathetic  and  the  inferior  laryngeal  nerve 

is  plainly  seen. 


PARATHYROIDS  145 

the  main  trunk  of  the  artery.  Finally,  that  the  inferior  thyroid 
arterv  is  of  much  more  difficult  access  for  ligation  than  the  superior, 
and  on  the  whole  offers  more  dangers  than  the  ligation  of  the  superior 
thvroid  arterv,  and  again  that  its  main  trunk  or  its  branches  of 
division  mingle  sometimes  in  a  very  intimate  way  with  the  parathyroids 
and  especially  the  inferior  laryngeal  nerve  (Plate  X,  Fig.  2),  is  a 
reason  why  a  great  many  surgeons  a  priori  prefer  to  deal  with  the 
superior  artery  rather  than  with  the  inferior.  Hence  possibly  a  reason 
for  their  divergence  of  opinion. 

In  the  writer's  investigations  he  has  found  that  if  normal  glands 
onlv  are  taken  into  consideration,  the  difference  in  caliber  between 
the  superior  and  inferior  thyroid  arteries  and  the  difference  in  their  posi- 
tion are  only  slight.  This  I  have  had  the  opportunity  to  observe  time 
and  time  again  when  demonstrating  normal  anatomy.  In  2  per  cent,  of 
the  cases  the  inferior  thyroid  artery  is  found  absent.  In  that  case  a 
large  ima  artery  is  often  seen  to  take  its  place.  At  the  same  time  there 
is  a  huge  superior  thvroid;  obviously  this  anatomical  fact  is  an  ideal 
one  so  far  as  polar  ligation  is  concerned,  inasmuch  as  after  ligation  of  the 
upper  pole  the  lobe  would  be  robbed  of  its  greatest  source  of  blood 
supply.  In  pathological  thyroids  I  have  seen  the  superior  thyroid  decid- 
edlv  larger  than  the  inferior  thyroid,  and  vice  versa.  I  have  the  impres- 
sion, however,  that  in  simple  goiters,  especially  those  of  large  size,  the 
inferior  thyroid  artery  is  decidedly  larger  than  the  superior,  whereas  in 
thyrotoxic  goiters  the  superior  seems  to  have  a  larger  caliber. 

Parathyroids. — In  animals,  especially  in  dogs  and  cats,  the  parathy- 
roids are  internal,  namely,  are  situated  in  the  parenchyma  itself  of  the 
gland.  In  man  the  parathyroids  are  external;  they  are  nearly  always 
located  outside  of  the  glandular  capsule.  Some  aberrant  parathyroid 
tissue,  however,  may  be  found  in  the  thyroid  parenchyma.  Getzowa 
states  that  when  a  superior  parathyroid  is  missing  it  is  nearly  always 
replaced  by  intraglandular  parathyroid  tissue.  While  working  in  the 
pathological  laboratory  at  Lausanne,  Switzerland,  with  my  master,  Pro- 
fessor Stilling,  I  made  the  examination  of  75  cadavers  in  order  to  deter- 
mine the  number  and  position  of  the  parathyroids.  I  found:  4  turns,  1 
parathyroid  (twice  the  upper,  and  twice  the  lower);  32  times,  2  para- 
thyroids; 26  times,  3  parathyroids;  11  times,  4  parathyroids;  2  times, 
no  parathyroids  at  all,  but  instead,  some  parathyroid  tissue  diffusely 
imbedded  in  the  fat  and  areolar  tissue  throughout  the  entire  postero- 
internal region  of  the  thyroid  and  easily  recognizable  by  its  orange- 
yellow  color.  From  these  findings  it  follows  that  the  stereotyped  con- 
ception of  two  superior  and  two  inferior  parathyroids  is  tar  from  being 
correct.  In  the  cases  where  I  found  only  1  parathyroid,  this  little 
glandule  had  apparently  undergone  a  compensatory  hypertrophy  as  all 


441)      TECHXIC  OF  OPERATIONS   UPOX   THE  THYROID  GLAXD 

four  times  thev  were  larger  than  they  usually  are.  One  of  them  was  not 
far  from  the  size  of  a  pea. 

With  what  we  physiologically  know  of  the  parathyroids  it  is 
difficult  to  accept  the  opinion  that  the  parathyroids  may  be  totally 
absent.  MacCallum  is  quite  correct  when  he  says,  "Because  in  a  space 
extending  from  the  basis  of  the  skull  to  the  diaphragm  we  do  not  find  a 
little  gland  the  size  of  a  lentil,  have  we  the  right  to  deny  its  existence?" 
The  same  author  concludes  that  the  number  of  parathyroids  is,  as  a 
rule,  in  direct  proportion  to  the  patience  and  persistence  of  the  searching 
anatomist. 

If,  on  the  one  hand,  the  parathyroids  may  be  diminished  in  num- 
ber, thev  mav,  on  the  other  hand,  be  found  more  numerous  than  nor- 
mally; for  instance,  Harvier,  Thompson  and  Harris  found  5  parathy- 
roids; Schaper  and  Berkeley,  6;  Getzowa,  7;  Zuckerkandl,  8;  and 
Erdheim,  12. 

While  the  position  of  these  glandules  may  van',  their  variation  is 
within  certain  definite  limits.  The  superior  parathyroids  are  more  con- 
stant in  position  than  the  inferior  ones.  The  superior  parathyroids  are 
found,  one  on  each  side,  in  the  vertical  groove  between  the  esophagus 
and  the  thyroid  at  the  junction  of  the  upper  third  with  the  two  lower 
thirds  of  the  thyroid  gland  (Fig.  71,  and  Plate  X,  Fig.  2);  this  is  about 
at  the  level  of  the  cricoid  cartilage.  As  a  rule  they  are  wholly  outside 
of  the  glandular  capsule.  The  arterial  branches  and  the  inferior  laryn- 
geal nerve  pass  up  in  front,  and  internally  to  them.  The  inferior  para- 
thyroids lie  generally  more  laterally  than  the  superior  ones.  They  are 
found  at  the  junction  of  the  lower  third  with  the  two  upper  thirds  of 
the  thyroid  and  are  external  to  the  inferior  laryngeal  nerve  and  the 
inferior  thyroid.      (Fig.  71  and  Plate  X,  Fig.  2.) 

Of  course  a  great  many  variations  are  met  with,  especially  for  the 
inferior  parathyroids.  They  may  be  found  at  the  extremity  of  the  lower 
pole,  under  the  lower  border  of  the  isthmus,  in  the  pre-  or  peritracheal 
fatty  tissue,  or  even  imbedded  in  the  thymus  gland. 

After  the  careful  researches  of  Evans,  Halstead,  Ginsberg,  Welsh, 
Geiss,  etc.,  we  know  that  the  parathyroids  get  their  blood  supply  from 
a  branch  of  division  of  the  inferior  thyroid  artery  through  a  small  vessel 
which  is  called  the  parathyroid  artery  and  which  supplies  both  the 
superior  and  inferior  parathyroids.  Only  rarely  the  superior  thyroid 
artery  gives  ofF  a  branch  destined  for  the  superior  parathyroids:  in  such 
instances  these  two  small  parathyroid  arteries,  the  one  destined  for  the 
superior  parathyroid  and  the  other  destined  for  the  inferior  parathyroid, 
may  anastomose  together.  Not  so  infrequently  both  superior  and 
inferior  parathyroids  get  their  blood  supply  independentlv  from  a  small 
collateral  bloodvessel  coming  off*  directly  from  the  posterior  longitudinal 


RECURRENT  LARYNGEAL  NERVES  447 

anastomosis  which  runs  on  the  inner  posterior  border  of  the  thyroid 
gland  and  connects  the  superior  with  the  inferior  thyroid  arterial  system. 

It  had  been  thought  for  a  time  that  there  was  no  other  source  of 
blood  supply  than  the  one  given  by  the  parathyroid  artery;  consequently 
if  these  little  glandules  were  deprived  of  their  only  known  blood  supply, 
thev  would  not  get  any  nourishment  from  another  source;  their  fate 
would  be  the  same  as  that  of  a  transplanted  gland.  This  is  not  quite 
correct.  We  know  that  there  exists  between  the  parathyroid  and  the 
thyroid  capsule  a  fine  collateral  circulation.  Another  collateral  circu- 
lation especially  for  the  superior  parathyroids  is  secured  by  fine  arteries 
coming  from  the  pharynx,  esophagus,  trachea.  Furthermore,  Ginsberg 
has  shown  that  the  secondary  blood  supply  for  the  parathyroid  glands 
is  secured  by  anastomotic  channels  from  the  opposite  side.  The  impor- 
tance of  this  collateral  circulation  is  too  obvious.  It  allows  us  to  hgate 
the  four  thyroid  arteries  without  running  too  great  risk  of  parathyroid 
insufficiency.  These  facts  are  in  perfect  concordance  with  our  clinical 
experience.  It  is  true  that  twice  tetany  has  occurred  as  a  consequence 
of  the  ligation  of  the  four  thyroid  arteries.  These  two  cases  were  reported 
by  Kocher  and  von  Eiselsberg.  They  are  the  only  two  cases  recorded. 
Why  this  occurred,  no  one  knows.  Possibly  there  were  some  vascular 
anomalies,  possibly,  too,  the  parathyroids  of  the  other  side  were  absent 
and  the  only  one  or  two  glandules  present  were  inadvertently  trauma- 
tized. Perhaps  these  patients  were  already  in  a  state  of  latent  hypopara- 
thyroidism: some  slight  disturbance  in  their  anatomical  or  functional 
equilibrium  was  sufficient  to  throw  out  of  gear  the  entire  parathyroid 
mechanism.  Whatever  the  cause  may  have  been,  similar  consequences 
have  not  been  reported  since.  De  Quervain  who  has  performed  quite 
often  the  ligation  of  3'.  out  of  4  thyroid  arteries,  namely,  the  two 
inferiors,  one  superior  and  the  anterior  branch  of  the  other  superior, 
has  never  noticed  any  signs  of  tetany. 

Recurrent  Laryngeal  Nerves.  -The  inferior  or  recurrent  laryngeal 
nerve  is  the  motor  nerve  of  the  larynx.  It  is  a  branch  of  the  vagus  nerve. 
It  arises  on  the  right  side  in  front  of  the  subclavian  artery,  winds  from 
before  backward  around  that  vessel,  and  ascends  obliquely  to  the  side 
of  the  trachea  behind  the  common  carotid,  and  either  in  front  of  <>i 
behind  the  inferior  thyroid  artery.  On  the  left  side  it  arises  in  front  of 
the  arch  of  the  aorta  and  winds  from  before  backward  around  the  aorta 
at  the  point  where  the  impervious  ductus  arteriosus  is  attached  and  then 
ascends  to  the  side  of  the  trachea.  I  he  nerve  on  each  side  ascends  in 
the  groove  between  the  esophagus  and  the  trachea,  passes  either  anteri- 
orly or  posteriorly,  or  more  often,  between  the  branches  <>t  division  of  the 
inferior  thyroid  artery  (Plate  IX,  Fig.  2),  enters  the  larynx  behind  the 
articulation  of  the  inferior  horn  of  the  thyroid  cartilage  with  the  cricoid, 
being  distributed  to  all  the  muscles  of  the  larynx  except  the  cricothyroid. 


448      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

These  anatomical  considerations  show  that  the  inferior  laryngeal 
nerve,  too,  lies  in  the  "danger  zone,"  namely,  the  postero-internal 
portion  of  the  thyroid  gland. 

Conclusions  Drawn  from  Anatomical  Facts. — I.  The  postero-internal 
surface  of  the  thyroid  gland  must  be  considered  as  the  danger  zone;  there 
are  found  the  parathyroids  and  the  inferior  laryngeal  nerves  (Fig.  71). 

2.  The  surgical  capsule  should  be  detached  and  retracted  just  enough 
to  allow  the  different  steps  of  the  operation  to  be  performed  easily,  and 
especially  the  luxation  of  the  goiter.  This  capsule  should  be  left  in  situ 
and  in  its  relations  with  the  thyroid  in  the  entire  postero-internal  region 
of  the  gland,  and  the  luxation  of  the  goiter  should  not  be  pushed  too  far 
(Plate  XXI),  so  as  not  to  disturb  the  collateral  circulation  between  the 
parathyroid  glandules  and  the  neighboring  tissues,  and  further  not  to 
run  the  risk  of  injuring  the  inferior  laryngeal  nerve. 

3.  Ligation  of  the  inferior  thyroid  artery  should  be  done  far  from 
its  point  of  entrance  into  the  thyroid  gland  (Plate  XXI).  The  "ultra- 
ligation"  of  Halstead  is  a  dangerous  method.  It  should  be  remembered 
that  not  so  infrequently  the  parathyroids  are  situated  between  the 
branches  of  bifurcation  of  this  artery,  consequently  if  ligation  takes 
place  near  the  glandular  capsule  the  parathyroids  are  exposed  to  injury. 
The  same  is  true  for  the  recurrent  laryngeal  nerve. 

4.  Total  unilateral  intracapsular  excision  of  the  thyroid  should  be 
discarded  because  of  the  danger  of  injuring  the  parathyroids  and  inferior 
laryngeal  nerves  (Plate  X,  Fig.  1).  Resection  is  the  method  of  choice, 
as  it  leaves  a  more  or  less  thick  sheath  of  glandular  tissue  in  connection 
with  the  danger  zone.  A  well-managed  enucleation  does  not  expose  to 
injury  the  parathyroids. 

5.  The  collateral  circulation  with  the  neighboring  tissues  is  so  well 
developed  for  the  thyroid  and  for  the  parathyroids  that  ligation  of  the 
four  arteries  can  be  performed  without  running  any  risks  of  tetany, 
provided  that  the  "danger  zone"  is  left  undisturbed. 

EXCISION,    RESECTION,    OR    ENUCLEATION? 

As  in  any  other  surgical  field,  the  surgeon  doing  thyroid  surgery 
must  have  at  his  disposal  several  technical  methods  in  order  to  be  able 
to  meet  all  emergencies  successfully.  He  must  adapt  his  technic  to  the 
case  and  not  suit  his  case  to  his  technic.  As  De  Quervain  says,  "It  is 
no  longer  enough  to  know  what  should  be  done  in  a  general  way,  but 
what  should  be  done  in  each  particular  case."  In  doing  thyroid  surgery 
to  what  method  shall  we  resort  ?  Shall  we  adopt  excision,  resection, 
enucleation,  as  the  method  of  choice,  or  shall  we  use  a  combination  of 
these  methods  ?     In  going  over  the  medical  literature  one  cannot  but 


EXCISIOX,  RESECTIOX,  OR  ENUCLEATION 


449 


be  impressed  by  the  confusion  which  exists  in  the  denominations  of  the 
different  surgical  procedures.  Nearly  always  the  terms,  excision,  enuclea- 
tion, resection,  thyroidectomy,  lobectomy,  extirpation  of  the  thyroid, 
are  used  indiscriminate!)". 


Fig.  72. — Intracapsular  excision. 

Excision. — Excision  was  used  by  Kocher  to  demonstrate  the  complete 
removal  of  one  lobe  without  leaving  anything  of  the  posterior  portion 
of  the  gland  (Fig.  72).  Excision  can  be  unilateral  or  bilateral;  total 
excision  can  take  place  only  in  malignant  goiters. 


Figs.  73  :uu\  74.     Transglandular  resection. 

Resection  (Mikulicz)  means  the  partial  extirpation  of  the  thyroid, 
a  portion  of  the  glandular  tissue  being  left  in  situ.  Resection,  too,  may 
be  unilateral  or  bilateral  I  Figs.  7^  and  74). 

29 


450      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

Enucleation  (Porta  and  Socin)  means  the  peeling  off,  the  decortica- 
tion of  one  or  several  intraglandular  nodules  (Figs.  75  and  76). 

The  other  denominations  as  thyroidectomy,  lobectomy,  hemithy- 
roidectomy,  have  only  a  general  meaning.  They  do  not  convey  in  any 
way  the  idea  of  how  the  removal  of  the  goiter  is  being  done,  namely,  if 
excision,  resection,  or  enucleation  has  taken  place.  Consequently  I 
shall  use  them  when  speaking  in  a  general  way  of  the  fact  that  an  opera- 
tion has  been  performed  on  the  thyroid  without  trying  to  indicate  pre- 
cisely the  mode  in  which  this  operation  has  been  performed. 


Figs.  75  and  76. — Enucleoresection. 


Inasmuch  as  excision  exposes  too  easily  to  injury  the  inferior  laryn- 
geal nerves  and  parathyroids,  this  method  has  been  more  or  less  aban- 
doned as  such.  Kocher  still  advocates  it  and  practises  it,  but  leaves  a 
small  portion  of  glandular  tissue  in  contact  with  the  danger  zone,  conse- 
quently, properly  speaking,  this  surgical  procedure  is  no  longer  a  true 
excision,  but  becomes  a  resection.  The  intracapsular  or  subcapsular 
excision  which  is  performed  by  some  of  our  American  surgeons,  and 
which  may  be  compared  to  a  total  decortication  of  the  lobe  is,  too,  for 
the  same  reasons  to  be  discarded.  (Plate  X,  Fig.  1.)  Not  very  long  ago 
saw  one  of  our  foremost  surgeons,  when  performing  this  intracapsular 
excision,  come  in  contact  with  a  parathyroid,  crush  it  with  a  hemostat, 


EXCISIOX,  RESECTIOX,  OR  EXUCLEATIOX 


451 


and  become  aware  of  it  only  when  his  attention  was  called  to  it  bv  one  of 
his  assistants.    Iversen  reports  a  case  operated  bv  Rowsing  in  which  both 


I  [GS.  77  and  jH.-    Cuneiform  resection. 


parathyroids  were  accidentally  removed  with  the-  excised  lobe,  although 

intracapsular  excision    was   undertaken   with    tin-  special   view    of  safe- 
guarding the  parathyroids  and  inferior  laryngeal  nerves.     Halstead  in  40 


452      TECH  NIC  OF  OPERATIONS   UPON   THE  THYROID  GLAND 

subcapsular  excisions  removed  one  or  two  parathyroids  with  the  excised 
lobe  only  J  times  !  These  accidents,  of  course,  would  never  have  occurred 
if  resection  had  been  performed.  There  may  have  been  an  error  in  technic; 
they  should  have  remained  intracapsularly.  Theoretically  this  may  be 
true;  practically,  however,  it  is  not  so  easy,  as  the  glandular  capsule  is 
thin  and  breaks  easily.  A  thick  layer  of  glandular  tissue  should  have 
been  allowed  to  remain  in  contact  with  the  danger  zone.  Not  only 
does  it  protect  the  patient  against  injury  of  the  inferior  laryngeal  nerve 
and  parathyroids,  and  save  the  surgeon  great  annoyance,  but  it  has  also 
a  great  cosmetic  value;  furthermore,  if  later,  another  operation  on  the 
other  lobe  should  become  necessary,  the  chances  for  hypothyroidism 
will  be  greatly  lessened. 

Resection  is  the  method  of  choice  as  it  fulfils  better  than  any  other 
method  all  the  requirements.  This  resection  may  be  either  cuneiform 
ox  frontal. 

The  cuneiform  resection  (Figs.  JJ  and  78)  advocated  in  1898  by 
Zoege  von  Manteuffel  is  made  in  the  following  manner:  After  the  pre- 
liminary ligation  of  the  superior  or  inferior  thyroid  arteries,  or  both 
together,  the  goiter  is  luxated;  the  imae  vessels  are  carefully  tied,  then 
an  oval  incision  extending  from  the  upper  to  the  inferior  pole  is  made 
into  the  glandular  capsule  and  the  parenchyma.  The  resection  is  then 
made  by  "wedging"  out  the  interior  of  the  gland.  The  amount  of  tissue 
removed  by  this  "melon-slice"  (Plate  XI)  method  is  suited  to  the 
necessity  of  the  case.  Great  care  should  be  taken  not  to  come  too  near 
the  parathyroids  and  the  inferior  laryngeal  nerves.  The  main  bleeding 
vessels  of  the  cut  surface  are  caught  and  tied,  then  a  continuous  mattress 
suture  of  plain  catgut  through  the  glandular  capsule  including  a  portion 
of  the  parenchyma  is  made.  (Plate  XII.)  If  the  cup-shaped  hole  is 
quite  deep,  two  rows  of  sutures  may  have  to  be  made,  one  intraparen- 
chymatous,  and  the  other  capsuloparenchymatous,  which  catches  the 
edge  of  the  capsule  and  rolls  the  two  edges  of  the  capsule  into  some 
semblance  of  a  normal  lobe.  (Plate  XII.)  Sutures  should  not  be  made 
too  snug,  as  otherwise  necrosis  of  the  sutured  portion  might  follow, 
especially  if  both  main  thyroid  arteries  have  been  tied.  This  method 
has  the  great  advantage  of  leaving  no  exposed  rough  glandular  surface 
afterward.  Care  should  be  taken  to  ligate  every  vein  of  the  glandular 
capsule  in  order  to  avoid  air  embolism,  and  postoperative  oozing. 

If  the  trans  frontal  resection  is  resorted  to  (Fig.  73),  and  this  will  be 
the  method  used  in  the  majority  of  cases,  it  is  done  in  the  following 
manner:  After  having  ligated  the  upper  poles  and  starting  at  the  upper 
pole,  hemostats  are  placed  all  the  way  along  the  external  border  of  the 
gland  and  then  the  parenchyma  is  cut.  Next  the  operator  proceeds 
from  outward  inwardly  on  a  frontal  plane,  aiming  to  reach  the  lateral 


™ 

a 


i 


^ 


Technic  of  Cuneiform    Resection. 
11k-  superior  thyroid  vessels  have  been  tied,  goiter  luxated,  and  a 
portion  of  the  thyroid  removed. 


melon-slice1 


PLATE    XII 


Technic  of  the  Cuneiform   Resection. 
I  he  gland  is  then  sewed  up  by  continuous  suture. 


EXCISION,  RESECTION,  OR  ENUCLEATION.  453 

surface  of  the  trachea,  thus  leaving  a  more  or  less  thick  glandular  portion 
in  contact  with  the  danger  zone.  The  rough  surface  which  remains  after 
resection  is  completed,  is  left  untouched;  no  effort  is  made  to  cover  it 
by  suturing  the  edges  of  the  glandular  wound  together  (Fig.  74). 

Resection  will  be  employed  in  even'  case  where  a  diffuse,  parenchy- 
matous enlargement,  thyrotoxic  or  not,  exists,  and  in  all  cases  of  diffuse 
colloid  degeneration. 

Enucleation,  as  such,  has  been  discarded  by  the  majority  of  surgeons, 
as  it  too  often  predisposes  to  relapses.  They  use  this  method  in  large, 
solitary,  colloid  and  cystic  goiters.  In  the  majority  of  cases,  however, 
enucleation  will  be  combined  with  partial  resection.  In  that  case  we 
shall  call  the  operation  enucleoresection.  Enucleation,  however,  should 
be  given  the  preference  over  the  resection  method  in  the  cases  where  the 
secreting  parenchyma  is  reduced  to  a  minimum.  In  such  instances  it 
is  absolutely  necessary  to  be  as  economical  as  possible  with  the  gland- 
ular tissue,  hence  the  indication  to  enucleate  instead  of  to  resect.  When 
one  has  to  be  parsimonious  with  the  thyroid  tissue,  it  is  better  not  to 
ligate  the  main  vessels  of  the  gland. 

Enucleation  finds  its  special  indications: 

1.  In  cases  where  there  is  a  large  but  single  cystic  or  colloid  nodule. 

2.  In  cases  of  complete  colloid  or  cystic  nodular  degeneration  of  the 
entire  gland.  In  such  conditions  a  radical  operation  is  not  to  be 
expected.  The  nodules  are  peeled  out,  one  after  another.  There  remain, 
of  course,  very  small  ones  which  cannot  be  enucleated,  and  which  will 
be  liable  to  relapse  later  on. 

3.  Enucleation  can  be  employed,  too,  in  cases  of  goiter  which  have 
relapsed. 

4.  If  a  nodular  goiter  takes  its  origin  in  the  postero-internal  region 
of  the  thyroid,  it  may,  after  it  has  reached  a  certain  development,  come 
in  contact  with  the  parathyroids  and  inferior  laryngeal  nerves.  Enuclea- 
tion in  such  cases  is  not  without  danger  for  these  organs.  Indeed,  a 
hemostat  put  on  a  bleeding  vessel,  or  a  ligature,  may  injure  the  recur- 
rent laryngeal  nerves  or  the  parathyroids.  It  is  consequentlv  better  in 
such  cases  to  leave  a  thin  portion  of  glandular  tissue  in  contact  with  the 
danger  zone,  even  if  that  portion  of  the  gland  has  undergone  goiterous 
degeneration.  Curiously  enough,  that  portion  of  the  goiter  will  revert 
to  a  normal  state,  and  seldom  will  cause  relapses. 

5.  Wlu-n  we  have  to  deal  with  a  multiple  nodular  goiter,  enucleo- 
resection is  the  method  of  choice  unless  there  should  be  some  special 
reasons  to  do  otherwise,  because  if  enucleation  only  is  employed,  the 
most  of  the  intra-nodular  thin  bands  of  glandular  tissue  which  are  still 
physiologically  active,  are  caught  in  the  sutures  and  ligatures  and  undergo 
fibrosis.  Consequently  the  purpose  for  doing  enucleation  is  defeated, 
hence  it  is  better  to  combine  it  with  resection. 


454      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

The  technic  for  enucleation  is  extremely  simple.  An  incision  is 
made  over  the  glandular  capsule  and  into  the  parenchyma,  until  the 
nodule  is  reached.  This  nodule  is,  as  a  rule,  easily  recognizable  on 
account  of  its  harder  consistency,  paler  color,  and  diminished  vasculari- 
zation. The  proper  plane  of  cleavage  is  then  sought;  when  it  is  found 
the  nodule  is  peeled  off  very  easily.  The  main  thing  is  to  start  decortica- 
tion only  when  one  is  certain  to  be  in  the  proper  plane  of  cleavage;  as 
long  as  there  is  doubt,  one  can  rest  assured  that  the  proper  plane  of 
cleavage  has  not  been  found.  One  does  not  need  to  fear  the  hemor- 
rhage which  takes  place  all  over  the  entire  surface  of  the  shell  left  after 
the  removal  of  the  nodule,  as  it  is  mostly  a  parenchymatous  hemorrhage. 
If,  however,  an  artery  of  some  consequence  should  bleed,  the  pouch  can 
be  everted  and  the  bloodvessel  clamped  and  hgated.  Then  a  continuous 
purse-string  suture  starting  internally  at  the  bottom  of  the  pouch  brings 
its  walls  into  close  contact  and  ipso  facto  removes  any  possibility  of  any 
further  hemorrhage.  Finally,  a  continuous  suture  of  the  glandular  cap- 
sule terminates  the  operation  on  the  thyroid  itself. 

SHALL    THE    OPERATION    BE    UNILATERAL    OR    BILATERAL? 

Shall  the  operation  be  unilateral,  or  bilateral  as  advocated  by  Mikulicz 
and  Kausch  ?  Of  course  this  question  applies  only  to  the  cases  in  which 
the  thyroid  is  bilaterally  affected.  It  would  not  enter  into  anyone's 
mind  to  advocate  a  bilateral  operation  unless  there  is  a  pathological 
reason  for  it  on  both  sides.  The  question  being  so  understood,  I  say, 
"Yes,  the  operation  should  be  bilateral  whenever  it  is  necessary  and 
whenever  the  condition  of  the  patient  warrants  it,  no  matter  if  we  deal 
with  a  simple  or  thyrotoxic  goiter."  In  the  beginning  of  my  surgical 
activity,  I,  too,  was  a  devotee  of  the  unilateral  resection  as  still  prac- 
tised today  by  the  majority  of  surgeons.  But  in  following  my  own  and 
other  surgeons'  cases,  in  which  unilateral  resection  had  been  performed, 
I  soon  recognized  the  fact  that  this  method  was  unsatisfactory,  espe- 
cially from  an  esthetic  and  relapse  stand-point.  Consequently,  I  gave 
it  up  and  resorted  to  bilateral  operations.  Indeed,  in  bilateral  patholog- 
ical conditions  of  the  thyroid  this  method  is  the  only  logical  one.  Take, 
for  instance,  a  multiple  nodular  goiter  developed  in  both  lobes.  There 
is  here  really  no  sense  in  removing  the  goiterous  nodules  only  on  one 
side  and  leaving  the  others  in  the  lobes,  as  these  nodules  are  bound  to 
grow  and  form  another  goiter.  Sooner  or  later  symptoms  will  reappear, 
and  with  them  the  dissatisfaction  of  the  patient  and  the  disappointment 
of  the  surgeon.  From  the  esthetic  point  of  view  nothing  has  been 
gained  by  the  unilateral  resection,  as  one  side  of  the  neck  is  still  puffed 
up,  while  the  side  where  the  operation  has  taken  place  shows  a  depression. 


SHALL   THE  OPERATION  BE   UX I  LATERAL  OR  BILATERAL     155 

Let  us  consider  a  diffuse  colloid  degeneration  of  the  entire  gland. 
Here,  again,  why  confine  the  surgical  act  to  one  side  onlv  ?  Even  if  a 
concomitant  resection  of  the  isthmus  takes  place,  there  still  remains  a 
diffuse,  colloid  degeneration  in  the  other  lobe.  Here,  again,  the  opera- 
tion is  insufficient;  the  functional  as  well  as  the  mechanical  disturbances 
have  been  only  partly  eliminated;  the  cure  cannot  be  complete,  relapses 
will  occur.     If  such  is  the  case  why  not  resect  bilaterally : 

In  dealing  with  a  diffuse,  non-toxic  vascular  goiter,  the  same  reasons 
which  have  been  invoked  for  resecting  other  goiters  bilaterally  still  stand 
good.  A  bilateral  resection  should  be  done  instead  of  leaving  a  large 
vascular  parenchymatous  goiter  on  one  side. 

But  it  is  especially  in  the  thyrotoxic  parenchymatous  goiter  that 
bilateral  resection  finds  its  special  indications.  There,  unless  special 
contra-indications  are  present,  the  necessity  for  bilateral  resection  is  an 
imperative  one.  In  the  great  majority  of  cases  one-sided  lobectomy  is 
insufficient  to  put  a  stop  to  hyperthyroidism.  The  patient  is  greatlv 
benefited,  yet  not  cured.  The  reason  is  because  there  is  still  too  much 
thyrotoxic  secreting  gland  left.  Even  ligation  of  the  upper  pole  of  the 
lobe  left  untouched  is  insufficient.  That  patient  belongs  to  the  class 
called  by  Kocher  "nicht  fertig  operiert."  Why  not  then  from  the  start 
resort  to  bilateral  resection?  Functionally  the  results  will  be  far  better; 
esthetically  they  will  be  perfect. 

Bilateral  resection  has  the  great  advantage  of  affording  a  general 
view  of  the  whole  gland.  This  is  indeed  important.  Despite  the  most 
careful  and  skilful  clinical  examination,  who  can  be  certain  in  every 
case  before  operation  that  a  lobe  is  normal  or  not  and  to  what  extent  it 
is  damaged.  Every  surgeon  has  had,  I  am  sure,  the  surprise  of  discov- 
ering at  the  operation  only,  that  a  lobe  which  he  considered  as  normal 
was  not  so,  that  a  retrosternal  goiter  was  present  which  had  been  unsus- 
pected, etc.  Furthermore,  it  is  only  after  having  inspected  the  whole 
gland  that  a  surgeon  can  best  decide  how  much  gland  can  be  resected 
on  each  side,  and  what  the  nature  of  the  technic  will  be,  whether  resec- 
tion,  enucleation,  or  enucleoresection   must  be   resorted   to. 

At  first,  one  might  thmk  that  relapses  must  be,  theoretically  at  least, 
more  frequent  with  bilateral  resection  than  with  unilateral  excision. 
Indeed,  with  the  latter  method,  the  whole  lobe  having  been  removed, 
with  the  exception  of  a  thin  band  of  the  posterior  layer,  relapse  can 
hardly  be  expected,  while,  with  the  bilateral  resection,  as  a  thick  portion 
of  glandular  tissue,  normal  or  nor,  is  left  /';/  situ  the  chances  tor  relapse 
are  greater.  Consequently  one  might  naturally  conclude  that  uni- 
lateral excision  is  to  be  given  the  preference:  goiter  developing  in  the 
non-operated  side  must  not  be  regarded  as  ;i  relapse,  but  is  a  new  goiter 
whose-  appearance  cannot  be  charged  to  the  method. 


456      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

The  argument  retains,  of  course,  its  full  strength  whenever  the  lobe 
left  untouched  is  normal.  In  that  case  if  any  goiter  occurs,  it  must  not 
be  regarded  as  a  relapse,  but  as  a  new  growth.  There  cannot  be  any 
doubt  about  that.  But  in  the  great  majority  of  cases  things  are  not  so: 
the  pathological  condition  is  not  confined  to  one  lobe  only;  as  a  rule 
both  lobes  are  involved,  one  perhaps  less  markedly  so  than  the  other, 
nevertheless,  they  are  both  affected.  Consequently  that  method  is  to 
blame  which  does  not  try  to  remedy  the  whole  condition  and  which 
leaves  purposely,  knowingly,  and  carelessly,  a  goiter,  no  matter  how 
small,  on  one  side.  An  error  of  "omission"  is,  nevertheless,  an  error 
and  should  be  charged  with  its  consequence. 

One  thing  has  struck  me  very  forcibly:  it  is  the  fact  that  after  bilat- 
eral resection  a  diffuse  parenchymatous  or  a  colloid  gland,  toxic  or  not, 
has  little  tendency  to  relapse.  It  seems  that  after  an  operation  the 
gland  readjusts  itself  and  reverts  to  the  normal  type. 

Of  course  if  the  patient's  condition  is  not  good,  if  it  is  taking  too 
great  risk  by  resecting  bilaterally,  this  operation  must  not  be  attempted; 
ligation  of  one,  two,  or  three  arteries  should  be  given  the  preference; 
unilateral  resection  should  be  resorted  to  until  the  patient's  condition 
warrants  the  attempt  on  the  other  side. 

In  conclusion  we  can  say  that: 

i.  Bilateral  resection  is  the  method  of  choice,  whenever  it  is  necessary 
and  possible; 

2.  It  affords  a  general  view  of  the  entire  gland  and  does  not  let  any 
goiter  escape  unobserved; 

3.  This  method  is  much  less  apt  to  give  relapse  than  the  unilateral 
resection; 

4.  From  an  esthetic  point  of  view  it  is  ideal; 

5.  Technically  the  method  is  very  simple.  In  fact,  it  is  much 
simpler  than  the  unilateral  intracapsular  excision  and  the  risks  of  injur- 
ing the  inferior  laryngeal  nerves  and  the  parathyroids  are  certainly  far 
less,  provided,  that  a  layer  of  thick  enough  glandular  tissue  is  left  in 
contact  with  the  danger  zone.  The  amount  of  hemorrhage  is  not  materi- 
ally larger  than  with  enucleation  or  unilateral  excision,  provided  pre- 
liminary ligations  of  the  main  arterial  trunks  have  been  made,  and 
provided,  too,  that  the  glandular  tissue  is  cut  only  after  being  clamped 
with  two  hemostats. 

6.  When  unilateral  resection  only  is  made,  whenever  there  is  a  slight 
amount  of  thyrotoxicosis,  or  whenever  bilateral  resection  must  be 
deferred  on  account  of  the  patient's  condition,  it  is  well  to  throw  a 
ligation  around  the  upper  pole  of  the  lobe  which  is  left  untouched. 


HOW  MUCH   THYROID   TISSUE  CAN  SATELY  BE  REMOVED   457 

HOW   MUCH    THYROID    TISSUE    CAN    SAFELY    BE    REMOVED? 

It  seems  that  even'  surgeon  has  his  own  rule.  Yon  Eiselsberg  leaves 
a  portion  of  glandular  tissue  which  can  be  compared  in  size  to  a  hen's 
egg.  Mikulicz  leaves  on  each  side  a  quantity  amounting  to  the  size  of 
a  walnut.  Riedel  is  satisfied  if  he  leaves  one-tenth  of  the  whole  gland, 
while  in  bilateral  goiters  he  leaves  one-third  of  one  lobe.  Hoennicke, 
considering  that  the  normal  weight  of  the  thyroid  is  in  the  neighborhood 
of  20  to  25  grams,  makes  it  a  point  to  leave  in  situ  enough  gland 
to  equal  about  this  weight.  De  Quervain  leaves  enough  thyroid  tissue 
so  as  to  equal  the  volume  of  the  normal  thyroid  gland.  Kocher  claims 
that  whenever  the  thyroid  shows  a  diffuse  parenchymatous  degenera- 
tion one-fourth  of  the  total  volume  of  the  gland  should  be  left  in  situ. 
Mayo  says  that  an  entire  lobe,  the  isthmus  and  the  two  lower  thirds  of 
the  other  lobe  can  be  safely  removed.  Kausch  leaves  one  and  one-half 
times  the  size  of  the  normal  thyroid. 

It  is  obvious  that  these  more  or  less  theoretical  rules  cannot  be 
applied  to  even'  case,  as  it  would  be  erroneous  to  believe  that  a  certain 
amount  of  pathological  glandular  tissue  has  the  same  physiological 
power  as  an  equal  amount  of  normal  thyroid  tissue.  It  is  consequentlv 
wrong  to  set  down  a  uniform  rule  which  should  be  applied  in  every 
case.  It  is  obvious,  too,  for  instance,  that  if  a  patient  with  diffuse  col- 
loid goiter  shows  symptoms  of  hypothyroidism,  this  thyroid  insuffi- 
ciency is  bound  to  become  more  marked  after  a  certain  portion  of  the 
gland  has  been  removed.  It  would  consequently  be  a  mistake  to  remove 
in  such  cases  as  much  thyroid  tissue  as  in  a  case  of  hyperthyroidism,  for 
instance.  In  the  former  case  all  that  we  want  is  to  relieve  the  patient  of 
his  pressure  symptoms,  and  to  relieve  him  of  his  deformity,  but  we 
should  have  constantly  in  mind  the  necessity  of  leaving  as  much  thy- 
roid tissue  as  can  possibly  be  done,  whereas  in  the  latter  case  the  func- 
tional activity  of  the  thyroid  being  what  we  are  trying  to  diminish,  we 
shall  feel  at  liberty  to  remove  a  far  greater  amount  of  thyroid  tissue 
than  in  the  former  case.  Furthermore,  it  should  always  be  borne  m 
mind  that  a  certain  amount  of  glandular  tissue  left  after  the  operation 
undergoes  resorption  on  account  of  the  vascular  disturbances  and  the 
organization  of  the  blood  clots  and  the  connective-tissue  formation  due 
to  the  sutures.  1  his  should  be  taken  into  consideration  when  deciding 
how  much  tissue  should  be  left.  One  might  expose  himself  to  disap- 
pointment if  he  should  count  too  much  on  the  so-called  "compensatory 
hypertrophy"  of  the  remaining  portion.  Halstead  seems  to  be  presently 
inclined  to  believe  that  this  compensatory  hypertroph}  is  onlj  a  process 
of  reaction  of  the  thvroid  to  a  low-grade  infection. 


458      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

We  may  consequently  conclude: 

1.  In  simple  goiter,  colloid  or  cystic,  multinodular  or  not,  without 
hypo-  or  hyperthyroidism  symptoms,  enough  thyroid  tissue  should  be 
left  on  each  side  so  as  to  equal  about  the  volume  of  half  of  a  normal  lobe. 

2.  If  hypothyroidism  symptoms  are  present,  the  amount  of  tissue 
left  must  be  in  proportion  to  the  degree  of  hypothyroidism  and  may 
equal  two  or  three  times  the  size  of  the  normal  lobe  on  each  side. 

3.  In  hyperthyroidism  to  leave  an  amount  equal  to  one-third  to 
one-fifth  of  a  normal  lobe  is  a  safe  procedure. 

SHALL   WE    DISSECT    THE    PARATHYROIDS? 

Some  surgeons  have  thought  that  they  would  avoid  injury  to  the 
parathyroids  by  dissecting  them  in  situ.  A  -priori  this  is  rational,  but 
the  results  obtained  have  not  been  encouraging.  Indeed,  when  dissect- 
ing a  cadaver,  if  we  stop  to  think  how  difficult  it  is  sometimes  to  iden- 
tify these  little  bodies,  how  little  they  differ  from  a  small  accessory 
thyroid  glandule,  from  small  lymph  glands,  or  even  from  small  fat 
nodules,  it  will  then  be  easily  understood  why  the  above-mentioned 
method  is  impractical.  It  would  necessitate  a  prolonged,  tedious,  and 
often  an  unsuccessful  operation;  it  would  expose,  furthermore,  to  trouble- 
some hemorrhages  by  injuring  the  numerous  veins  of  that  region  and 
would  have  too  often  as  a  result,  the  injury  of  the  organs  which  we 
are  trying  to  protect,  namely  the  inferior  laryngeal  nerves,  and  the 
parathyroids.  It  is  quite  plain  that  these  disadvantages  and  dangers 
add  to  those  of  a  prolonged  operation.  Consequently  any  method 
whose  aim  would  be  to  identify  de  visa  these  little,  too  often  hypo- 
thetical organs,  is  bound  to  be  unsatisfactory.  It  must  then  be  dis- 
carded. The  best  way  not  to  injure  the  parathyroids  is  to  ignore 
them  by  leaving  them  undisturbed  with  the  posterior  capsule. 

LIGATIONS. 

The  ligation  of  the  thyroid  arteries  in  goiter  was  already  utilized  by 
veterinary  surgeons  for  goiters  of  horses,  and  was  proposed  as  a  thera- 
peutic measure  in  human  surgery  by  von  Muys  in  1639  and  Langhe 
in  1707.  The  first  ligation  in  man  was  done  by  Blizzard  in  181 3  when 
he  tried  to  ligate  the  superior  thyroid  artery  in  order  to  cause  the 
atrophy  of  a  large  goiter.  The  patient  died  from  hemorrhage.  In  1814 
Walter  attempted  this  operation  again  and  succeeded.  The  ligation  of 
the  inferior  thyroid  was  done  for  the  first  time  by  Porter  in  1852  but  it 
was  only  in  1888  that  Wolfler  and  Rydigier  applied  this  method  systemat- 
ically to  goiter  surgery.  They  obtained  good  success  especially  in  the 
vascular  and  parenchymatous  forms.     In  cancerous,  cystic,  fibrous,  and 


LIGATIONS  4.">!  I 

calcareous  forms  the  method  failed,  as  could  be  expected,  to  give  satis- 
faction. Later,  when  the  technic  became  better  worked  out  and  the 
antiseptic  era  protected  the  patients  against  infection,  these  ligations 
were  given  up  and  replaced  by  thyroidectomy.  Today  they  are  used 
onlv  as  a  preliminary  step  to  thyroidectomy  in  Basedow's  disease. 

The  vasomotor  and  secretory  nerves  of  the  thyroid  penetrate  into 
the  thyroid  by  the  same  route  as  do  its  bloodvessels.  At  the  upper 
pole  small  branches  of  the  external  laryngeal  nerve,  which  itself  is  a 
branch  of  the  vagus,  penetrate  into  the  gland  with  the  superior  thyroid 
artery  as  well  as  the  sympathetic  branches.  At  the  inferior  pole  the 
nervous  branches  reaching  the  thyroid  gland  in  conjunction  with  the 
inferior  thyroid  artery  are  mostly  all  of  sympathetic  origin.  Accord- 
ing to  Bnau  these  branches  come  from  the  superior  middle  and  inferior 
cervical  sympathetic  ganglions  and  anastomose  freely  with  the  cardiac 
nerve  branches  of  the  vagus.  It  is  found  that  the  inferior  laryngeal 
nerve  sends  directly  to  the  thyroid  gland  a  very  few  small  filets  whose 
physiological  action  is  not  known. 

It  is  a  very  well-accepted  fact  today  that  the  branches  of  the  superior 
laryngeal  penetrating  the  thyroid  at  its  upper  pole  are  essentially  vaso- 
dilatatory:  this  has  been  demonstrated  plainly  by  Frank  and  Halhon. 
More  so,  according  to  Ascher-Flack  (Centralblatt  fur  Physiologie, 
June,  1910,  xxiv,  211-213),  the  irritation  of  the  peripheral  end  of  this 
nerve  produces  an  increased  secretion  of  the  thyroid;  consequently  the 
external  superior  laryngeal  is  not  only  a  vasodilatator}',  but  is  also  at 
the  same  time  an  excitosecretory  nerve.  The  central  irritation  of  the 
depressor  nerve  causes  an  intense  vascularization  of  the  thyroid  through 
a  reflex  intermediary  action  of  the  external  laryngeal  nerve.  The  action 
of  the  sympathetic  branches  are,  according  to  Frank,  Halhon  and  von 
Cyon,  vasoconstrictory.  Their  division  causes,  according  to  Missiroli 
(./rchivio  di  fisiologia,  1908,  vi,  582-594),  a  hypersecretion  of  the  thy- 
roid parenchyma.  If  this  is  really  so,  then  sympathectomy  for  Graves' 
disease  is  illogical;  at  any  rate  some  other  explanation  should  be  given 
in  order  to  explain  its  favorable  results  in  that  condition. 

In  the  light  of  the  above  considerations  it  follows  that  with  our 
ligations  we  nor  only  diminish  the  blood  supply  of  the  thyroid  gland, 
but  also,  at  the  same  time,  we  deprive,  to  a  certain  extent  at  hast,  the 
thyroid  of  its  nerve  supply.  In  fact,  our  ligations  should  be  considered 
as  true  angioneurotomies. 

If  we  sum  up  these  facts  and  the  ones  spoken  of  in  the  chapter 
on  The  Blood  Supply  of  the  Thyroid,  we  come  to  the  following 
conclusions : 

1.  With  our  ligations  we  not  only  dimmish  the  blood  supply  and 
consequently   the  secreting  power  of  the  thyroid,  but   we  act   directly 


460      TECH  NIC  OF  OPERATIONS   UPON  THE  THYROID  GLAND 

upon  the  gland  itself  by  determining  atrophy  of  the  territory  deprived 
of  the  blood  circulation.  This  atrophy  is  in  direct  proportion  to  the 
amount  of  blood  supply  suppressed.  It  causes  a  thickening  of  the  cap- 
sule and  an  interstitial  cirrhotic  process  invading  the  gland  throughout; 
the  epithelial  elements  have  the  tendency  to  revert  to  their  normal  type. 

2.  Since  the  external  laryngeal  nerve  has  a  marked  vasodilatatory 
and  excitosecretory  action  upon  the  thyroid,  and  since  the  sympathetic 
branches  penetrating  the  thyroid  with  the  superior  and  inferior  thyroid 
arteries  seem  to  be  less  important  physiologically,  it  follows  that  our 
efforts  should  be  directed  against  the  external  laryngeal  nerve.  This 
can  be  done  easily  at  its  point  of  entrance  into  the  gland,  namely,  at  the 
upper  pole,  by  performing  a  ligation  including  all  the  branches  of  divi- 
sion of  the  superior  thyroid  artery.  In  so  doing  all  the  branches  of  the 
external  laryngeal  nerve  are  bound  to  be  caught.  This  is  best  done  by 
the  polar  ligation  method  of  Stamm  and  Jacobson.  This  ligation  must 
be  double,  and  in  order  to  be  most  effective,  the  neurovascular  pedicle 
included  between  the  two  ligatures  must  be  severed  with  a  knife  or 
scissors.  In  that  way  the  branches  of  the  external  laryngeal  are  surely 
divided.     The  ligation  then  becomes  an  angioneurotomy. 

3.  Whenever  the  condition  of  the  patient  is  such  as  to  warrant  a 
ligation  only,  the  ligation  of  the  superior  pole  is  the  method  of  choice, 
because  to  the  suppression  of  the  vascular  supply  we  add  the  suppression 
of  the  nervous  supply  through  the  external  laryngeal  nerve. 

4.  If  the  condition  of  the  patient  warrants  a  double  ligation,  the 
ligation  of  the  superior  pole  and  of  the  inferior  thyroid  artery  on  the 
same  side  is  the  method  to  be  chosen.  Indeed,  as  the  anastomoses 
between  the  inferior  and  superior  thyroids  are  very  numerous,  whereas 
the  bilateral  anastomoses  are  very  much  less  developed,  the  maximal 
effect  will  be  obtained  if  we  obliterate  the  thyroid  arteries  of  the  same 
side  instead  of  ligating,  as  is  so  frequently  done,  both  superior  arteries. 

5.  For  the  same  reasons,  if  the  upper  pole  has  been  previously 
ligated  the  one  which  will  have  to  be  hgated  next  will  be  the  inferior 
thyroid  on  the  same  side. 

6.  If  three  ligations  are  performed  in  one  or  several  sittings,  two 
must  be  performed  on  the  same  side,  and  the  third  on  the  upper  pole  of 
the  opposite  side  so  that  there  will  finally  remain  one  thyroid,  the  inferior, 
to  ligate  if  one  chooses  to  do  so. 

7.  Ligation  of  the  four  thyroid  arteries  in  one  or  more  sittings  can 
be  done  without  danger  of  necrosis  of  the  thyroid  gland  and  without 
danger  of  tetany,  unless  vascular  anomalies  should  exist,  and  this  cannot 
be  foretold. 

Indications  for  Ligation. — One  of  the  greatest  advocates  for  this 
method  of  treatment  of  Basedow's  disease  is  Kocher.    As  he  said,  "If  we 


LIGA  TIONS  461 

ligate  one  arterv  onlv,  we  obtain  an  amelioration  of  the  patient's  con- 
dition; if  we  ligate  two  arteries  the  amelioration  is  greater;  if  to  it  we 
add  the  removal  of  one  lobe,  the  amelioration  is  still  greater.  If  the 
results  obtained  are  not  sufficient,  we  can  ligate  one  or  two  arteries  on 
the  other  side,  and  we  can  perform  another  partial  thyroidectomy  on 
the  lobe  which  has  not  been  touched."  These  views  have  since  been 
almost  universally  accepted  by  the  majority  of  operators.  In  advanced 
cases  successive  and  graduated  operations  are  the  method  of  choice. 
Ligation  alone  of  two  or  three,  or  even  of  four  arteries,  will  very  rarely 
suffice  to  cure  the  patient  who  is  seriously  ill  with  Graves'  disease. 
Although  considerable  improvement  may  follow,  thus  allowing  the  sur- 
geon to  perform  a  more  radical  operation,  a  complete  and  permanent 
cure  is  hardly  to  be  expected.  Ligations  must  always  be  practised  with 
the  view  of  improving  the  patient's  condition  so  as  to  allow  a  thyroidec- 
tomy to  be  safely  performed  later.  These  small  operations  have  the 
further  advantage  of  testing  the  patient's  resistance  to  the  operation; 
they  consequently  give  precious  indications  for  the  future  surgical  pro- 
cedures. In  light  forms  of  Graves'  disease  it  is  better  to  resort  to 
thyroidectomy  at  once  without  preliminary  ligations.  Ligations  must  be 
reserved  for  those  thyrotoxic  cases  where  thyroidectomy  cannot  be 
safely  undertaken. 

Ligations  are  clearly  indicated  in  those  forms  of  non-toxic  vascular 
goiters  in  which  the  essential  feature  is  an  enormously  increased  vascu- 
larization. Here  the  goiter  resembles  an  angioma  cavernosum  with  all 
its  vascular  symptoms,  abnormally  marked  blood  supply,  thrill,  systolic 
murmur,  partial  reductibility  by  compression,  etc.  1  hyrotoxicosis  may 
be  totally  absent.  This  is  the  struma  vasculosa  of  Kocher.  Ligations 
in  these  forms  of  struma  can  be  performed  in  one  sitting  and  can  In- 
applied  to  the  four  arteries.  A  complete  cure  may  be  hoped  for  by  tins 
simple  method. 

Ligations  art-  ordinarily  not  indicated  for  the  secondary  forms  of 
Graves'  disease-,  namely,  in  Basedowified  goiters.  In  these  cases  their 
efficacy  is  only  slight,  and  the  same  is  true  for  the  non-toxic  parenchy- 
matous goiters.  Exceptionally,  however,  if  in  certain  Basedowified  goiters 
the  vascular  symptoms  should  be  very  pronounced,  preliminary  ligations 
may  be  very  beneficial,  as  they  diminish  the  blood  supply,  and  what  is 
of  utmost   importance,  lessen  the  thyrotoxic  symptoms. 

There  are  cases  of  Basedow's  disease  apparently  of  nervous  origin 
and  characterized  clinically  by  the  absence,  or  almost  abs<  nee,  of  thy- 
roid physical  symptoms.  The  symptom-complex  stems  to  rake  appar- 
ently its  origin  in  an  intense  irritation  of  the  cervical  sympathetic  sys- 
tem. In  these  eases  ligations,  and  even  resections,  are  not  satisfactory. 
Resection  of  the  sympathetic  nerve  with  one  or  two  of  its  ganglia  seems 
to  be,  for  the  time  being,  the  method  <>t  choice. 


462      TECH  NIC  OF  OPERATIONS  UPON  THE  THYROID  GLAND 

After  one  ligation  has  been  made  the  patient  should  be  given  from 
two  to  six  months  rest;  then,  according  to  his  condition,  a  second,  and 
a  third,  ligation  may  be  performed.  From  three  to  five  months  are  then 
permitted  to  elapse  in  order  to  give  the  patient  a  chance  to  get  the  full 
benefit  of  these  operations.  Only  then,  and  that  is  if  the  condition  of 
the  patient  warrants  it,  may  thyroidectomy  be  performed;  otherwise 
the  fourth  artery  should  be  ligated.  In  cases  of  advanced  thyrotoxicosis 
in  which  the  organs  have  undergone  a  secondary  change,  such  as  neph- 
ritis, hepatitis,  myocarditis,  arrhythmia,  etc.,  the  dangers  of  an  opera- 
tion, whatever  it  might  be,  ligations  or  resection,  are  quite  great,  and 
the  hope  for  cure,  or  of  great  improvement,  is  only  slight. 

What  is  the  Point  of  Election  for  Ligation? — For  the  superior  thyroid 
artery  there  is  no  discussion.  This  ligation  takes  place  just  before  its 
entrance  into  the  upper  pole.  It  is  best  done  by  the  polar  method  of 
Stamm  and  Jacobson  (Plate  XIII,  Fig.  3). 

For  the  inferior  thyroid  artery  divergences  of  opinion  still  prevail. 
Some  surgeons  advocate  ligation  at  its  point  of  entrance  into  the  gland- 
ular capsule;  others  advocate  the  ligation  just  inwardly  of  the  vascular 
cord;  while  others  advocate  ligation  at  the  inner  border  of  the  scalenus 
anticus. 

Ligation  of  the  inferior  thyroid  artery  near  its  point  of  entrance  into 
the  thyroid  has  many  disadvantages.  It  necessitates  first,  the  dislocation 
of  the  goiter.  This  is  by  no  means  always  easy.  In  exophthalmic  goi- 
ter, hemorrhage  from  the  goiter  itself  occurs  easily  during  this  act,  on 
account  of  the  adhesions  with  neighboring  tissues,  and  because  of  the 
friability  of  the  bloodvessels.  Furthermore,  since  the  search  for  the 
artery  takes  place  in  the  penthyroidal  cellular  space,  which  we  know 
is  very  vascular,  this  search  for  the  artery  or  its  branches  in  that  region 
is  rendered  difficult  by  the  numerous  veins  found,  whose  injury  increases 
the  difficult)'  of  the  operation.  Furthermore,  we  must  not  forget  that  this 
region  constitutes  the  danger  zone  (Plate  IX,  Fig.  2)  which  must  be  abso- 
lutely avoided,  unless  one  wishes  to  run  the  risk  of  injuring  the  inferior 
laryngeal  nerve  and  the  parathyroids.  In  addition  to  this,  at  that  level, 
the  inferior  thyroid  artery  has,  as  a  rule,  already  undergone  division 
into  several  branches  so  that  one  often  ligates  only  a  branch  instead 
of  the  main  trunk;  the  small  parathyroid  artery  in  that  region  is 
bound  to  be  injured,  and  the  parathyroids  and  the  inferior  laryngeal 
nerve  are  so  interwoven  with  the  branches  of  division  of  the  inferior 
thyroid  artery  that  the  risk  of  injuring  them  is  great  (Plate  IX,  Fig.  2). 
In  the  light  of  all  these  considerations  ligation  of  the  artery  near  its  point 
of  entrance  into  the  thyroid  is  not  to  be  advocated.  The  same  is  true 
for  the  intracapsular  ligation,  as  practised  by  those  who  perform  thy- 
roidectomy by  the  decortication  method.  The  same  is  true  for  the 
"ultraligation,"  as  advocated  by  Halstead. 


PLATE    XIII 


Fig.  i. — The  skin  and  platysma  myoides  have  been  cut.  The  omohyoid  and 
sternohyoid  muscles  are  then  encountered.  They  are  divided  bluntly  at  their  point  of 
junction.  The  division  of  these  muscles  follows  the  same  direction  as  their  muscular 
fibers. 


Fig.  2. — The    upper   pole  of  the   thyroid   is  then   isolated. 


Fig.  3. — A  curved  thread  carrier  is  swung  around  the  upper  pole  and  ligation  is 
made  so  as  to  bite  off  a  little  of  the  thyroid  tissue.  Another  ligation  is  placed  a  little 
above  and  the  thyroid  wsstls  are  then  cut  between  the  two  ligatures. 


Figs.   1,  2  and  3. — Ligation  of  the    Upper  Pole. 


•  LIGATIONS  463 

The  point  of  election  for  ligating  the  inferior  thyroid  is  inwardly  of 
the  carotid  sheath,  soon  after  the  artery  has  crossed  it  transversely  and 
posteriorly  (Plate  IX,  Figs,  i,  2).  In  man)-  instances  the  thyroid  is  so 
hypertrophied  that  its  lateral  border  overlaps  the  vascular  cord.  Ligation 
of  the  artery  at  that  point  consequently  offers,  in  the  opinion  of  Delore 
and  Alamartine,  the  same  dangers  and  disadvantages  as  if  the  artery  were 
ligated  at  the  point  of  entrance  into  the  thyroid.  They,  for  this  reason, 
consider  the  ligation  of  the  artery  at  the  inner  border  of  the  scalenus 
anticus  as  the  method  to  be  followed.  (Plate  X,  Figs.  2  and  79.)  These 
conclusions  seem  to  me  not  quite  correct.  To  be  sure,  sometimes  the  thy- 
roid is  so  enlarged  as  to  render  this  ligation  very  difficult.  I  grant  that 
in  these  cases  the  method  for  the  ligation  of  the  inferior  thyroid  is  the 
one  they  propose.  This,  however,  is  not  common.  As  a  rule,  even  with 
voluminous  thyroids,  it  is  possible  to  retract  the  carotid  sheath  out- 
wardly and  the  thyroid  inwardly  so  as  to  allow  ligation  to  take  place 
without  too  great  difficulties.  If  luxation  of  the  goiter  can  be  performed, 
then  ligation  of  the  inferior  thyroid  can  surely  take  place  at  the  point 
of  election.  It  should  not  be  forgotten  that,  in  undergoing  enlargement 
the  thyroid  gland  does  not  carry  with  it  and  away  from  their  normal 
places,  the  parathyroids  and  the  inferior  laryngeal  nerves.  These  organs 
remain  where  they  are,  no  matter  how  large  the  goiter  may  become, 
whereas  the  carotid  sheath  is  displaced  laterally  and  posteriorly,  so 
that  in  reality  the  ligation  of  the  artery  just  inwardly  of  the  vascular 
cord  does  not  expose  these  organs  to  injury.  Another  advantage  of 
ligating  the  inferior  thyroid  artery  at  the  point  of  election  as  just  men- 
tioned, is  that  at  that  point  ligation  takes  place  outside  of  the  perithy- 
roidal  cellular  space.  This  lessens  the  danger  of  injuring  the  veins 
which  are  usually  found  in  it.  For  all  these  reasons  we  may  conclude 
that  the  point  of  election  for  the  ligation  of  this  thyroid  artery  is  just 
inwardly  of  the  vascular  cord  (Plate  XXI). 

In  ligating  the  artery  at  that  point  injury  to  the  inferior  laryngeal 
nerve  and  to  the  parathyroids  is  quite  out  of  the  question.  Furthermore, 
the  danger  of  injuring  the  veins  of  the  perithyroidal  cellular  space  is 
practically  nihil.  The  only  organ  which  might  be  injured  is  the  sympa- 
thetic nerve  with  its  middle  cervical  ganglion.  In  the  light  of  our  mod- 
ern views,  even  if  such  a  thing  should  happen,  the  patient  would  not 
be  the  worse  for  it.  1  even  think  that  in  many  instances,  inasmuch  as 
the  sympathetic  lies  just  behind  the  artery  imbedded  in  areolar  tissue, 
it  is  a  good  plan  to  add  to  the  ligation  the  resection  of  the  sympathetic 
nerve.     I  hat  is  precisely  what  I  sometimes  do. 

Technic  of  Ligations.  The  problem  whether  general  or  local  anes- 
thesia should  be  used  is  one  to  be  deeitled  with  each  individual  case. 
On  the  condition  ol  the  patient  depends,  too,  how  main  ligations  should 
be  dene  111  one  sit  ting. 


464      TECH  NIC  OF  OPERATIONS   UPON   THE  THYROID  GLAND 

The  polar  ligation  of  the  superior  pole  is,  as  a  rule,  an  easy  opera- 
tion and  quickly  done.  I  have  often  performed  it  while  the  patient  was 
still  in  bed,  in  order  to  reduce  to  a  minimum  the  amount  of  fear  and 
shock.  But  the  ligation  of  the  inferior  thyroid  is  a  more  complicated 
matter  because  it  is  of  more  difficult  access.  Some  authors  even  claim 
that  this  operation  is  as  serious  as  thyroidectomy  itself.  In  the  great 
majority  of  cases,  however,  this  assertion  is  certainly  exaggerated. 

Ligation  of  the  four  thyroid  arteries  in  one  sitting  should  seldom  be 
made  because,  if  the  patient's  condition  is  such  as  to  warrant  a  ligation 
of  the  four  arteries  at  the  same  time,  thyroidectomy  should  by  all  means 
be  preferred  to  ligations.  The  amount  of  fear  and  shock  will  not  be 
greater,  and  the  result  will  be  far  more  satisfactory  and  permanent. 
However,  if  one  should  choose  to  do  so,  either  because  he  has  to  deal 
with  a  struma  vasculosa,  or  for  any  other  reasons,  then  the  transverse, 
or  low-collar  incision,  made  in  the  usual  way  for  thyroidectomy,  should 
be  given  the  preference.  It  is  better  to  expose  the  gland  in  a  similar 
manner  just  as  if  thyroidectomy  were  to  be  performed;  the  two  upper 
poles  are  dissected  out  and  ligated.  The  same  is  done  for  the  inferior 
thyroid  arteries  on  both  sides. 

Isolated  Ligation  of  the  Superior  Pole. — A  transverse,  or  slightly 
oblique  incision  of  four  or  five  centimeters  is  made  laterally  to  the  thy- 
roid cartilage  at  the  level  of  its  superior  border,  and  if  possible,  in  a  skin 
crease.  As  in  the  large  majority  of  cases  the  superior  pole  is  easily  felt, 
the  latter  may  serve  as  a  landmark  for  the  place  where  the  incision  must 
be  made.  The  two  skin  flaps  are  retracted;  a  small  branch  of  the  super- 
ficial cervical  plexus  and  one  of  the  anterior  jugular  veins  may  be  encoun- 
tered. They  are  retracted.  The  omohyoid  and  sternohyoid  muscles 
are  then  prepared  and  separated  bluntly  in  the  direction  of  their  running 
fibers.  (Plate  XIII,  Fig.  i.)  The  fibers  of  the  sternothyroid,  which  he 
underneath,  are  divided  longitudinally,  bluntly  too,  and  well  retracted 
with  blunt  hooks.  The  upper  pole  is  thus  brought  into  view.  (Plate 
XIII,  Fig.  2.)  It  is  prepared,  doubly  ligated  with  silk  carried  by  a 
curved  ligature  carrier,  and  cut  between  the  two  ligatures.  (Plate  XIII, 
Fig.  3.)  One  should  always  have  in  mind  that  it  is  not  by  any  means 
difficult  to  miss  the  dorsal  branch  of  the  superior  thyroid  artery  while 
passing  the  ligature  around  the  upper  pole.  This  fact  may  sometimes 
account  for  the  failure  to  realize  an  expected  improvement  in  a  patient 
with  a  toxic  goiter  after  unilateral  or  bilateral  ligation  of  the  upper  pole 
was  thought  to  have  been  accomplished.  No  drainage;  one  or  two 
separate  sutures  for  the  muscles;  suture  of  the  platysma,  and  intradermic 
suture. 

Technic  for  the  Isolated  Ligation  of  the  Inferior  Thyroid  Artery. — Pre- 
cisely in  the  line  of  the  transverse  incision,  contemplated  for  future  thy- 


PLATE    XIV 


A<& 


Ligation  of  the  Inferior  Thyroid  Artery. 

I  his  operation  is  supposed  to  be  a  preliminary  step  before  attempting  thyroid- 
ectomy, hence  the  large  incision  made.  The  superficial  cervical  fascia  has  been 
divided  just  in  front  of  the  sternocleidomastoid  muscle.  This  muscle  is  retracted 
outwardly  while  the  prethyroid  muscles  and  the  thyroid  gland  are  retracted  inwardly. 
(The  picture  shows  a  portion  of  both  anterior  jugular  veins  missing.       This  is  an  error.) 


PLATE  XV 


Ligation  of  the   Inferior-  Thyroid  Artery. 
I  he  sternomastoid  and  the  muscular  capsular  space  have  been  entered.    The  carotid 
sheath  is  then  retracted  outwardly  while  the  prethyroid  muscles  and  the  thyroid  gland 
are  retracted  inwardly.    The  surgical  space  is  carefully  avoided.    The  inferior  thyroid  is 
then  located  and  tied. 


LIGATIONS  465 

roidectomy,  and  over  the  tendon  of  the  omohyoid  muscles,  a  transverse 
incision  of  6  to  8  cms.  is  made.  The  two  skin  flaps  are  retracted  upward 
and  inward.  Just  along  the  inner  border  of  the  sternocleidomastoid 
muscle  and  parallel  to  it  an  incision  is  made  on  the  fascia  covering  the 
prethyroid  muscles  (Plate  XI\);  then  the  finger  penetrates  bluntly 
between  the  sternocleidomastoid  and  the  prethyroid  muscles  so  as  to 
travel  through  the  sternocleidomuscular  plane  of  cleavage  until  the 
carotid  sheath  is  located.  The  sternocleidomastoid  muscle  and  the 
vascular  cord  are  then  retracted  laterally,  and  the  thyroid  gland  cov- 
ered with  its  prethyroid  muscles  is  retracted  inwardly  by  a  retractor 
especially  designed  for  the  purpose.  (Plate  XV.)  Great  care  should  be 
taken  not  to  open  the  surgical  capsule  of  the  thyroid.  A  finger  then  goes 
in  search  of  Chassaignac's  tubercle  or  the  anterior  tubercle  of  the 
transverse  process  of  the  sixth  cervical  vertebrae.  One  centimeter 
below  this  tubercle,  as  a  rule,  the  inferior  thyroid  artery  is  found,  its 
pulsations  facilitating  the  finding  of  it.  A  curved  blunt  thread  carrier 
with  a  small  radius  is  used  to  earn'  the  ligatures.  Care  should  be 
taken  in  handling  this  artery,  as  it  is  often  thin  and  friable,  and 
especially  so  in  Basedow's  disease. 

Sometimes  the  artery  is  not  found.  It  may  be  caught  by  the  assis- 
tant's retractors  and  compressed  so  as  to  prevent  its  pulsations  being 
felt,  but  release  of  this  pressure  will  soon  tell  as  to  its  presence.  If  at 
the  point  where  the  inferior  thyroid  is  supposed  to  be,  instead  of  finding 
an  artery  with  a  transverse  direction,  one  with  a  vertical  direction  is 
found,  then  we  have  to  deal  with  either  the  truncus  thyreocervicalis, 
or  with  the  ascending  cervical  artery.  This  is  a  precious  indication,  as 
it  will  help  to  find  the  inferior  thyroid  artery.  If,  however,  these 
researches  fail,  the  conclusions  must  be  reached  that  very  likely  this 
artery  is  absent. 

Isolated  Ligation  of  the  Inferior  Thyroid  on  the  Inner  Border  of  the 
Scalenus.  Dietrich  and  Langenbeck,  who  were  the  first  to  advocate  this 
method,  used  to  pass  between  the  two  heads  of  the  sternocleidomastoid 
muscle.  Drobnik,  Rudigier  and  \\  olfler  have  advocated  the  following 
method  (  Fig.  79) : 

I  wo  centimeters  above  the-  clavicle  and  about  0.5  cm.  behind  the 
posterior  border  of  the  sternocleidomastoid  muscle,  a  slightly  upward- 
curved  incision  ot  5  cms.  is  made.  I  he  superficial  cervical  fascia  is 
divided  and  if  the  external  jugular  vein  is  encountered,  it  is  clamped  and 
cut.  In  the  triangle  formed  by  the  sternocleidomastoid  muscle,  the  omo- 
hyoid and  the  clavicle,  a  blunt  dissection  takes  place  until  tin  scalenus 
amicus  is  found.  On  its  anterior  surface  lies  the  phrenic  nerve:  it  is 
retracted  inwardly  with  the  fat  tissues.  On  the  inner  border  of  the 
scalenus  the  inferior  thyroid  is  felt  pulsating  and  may  also  be  seen.  It 
30 


466      TECH  NIC  OF  OPERATIONS   UPON  THE   THYROID  GLAND 

is  ligated  between  the  two  ligatures  and  cut.  No  drainage;  intradermic 
suture.  This  operation  has  the  great  advantage  of  taking  place  far 
from  the  thyroid  gland  and  its  danger  zone.  It  causes  no  risks  of  tetany, 
of  injury  to  the  inferior  laryngeal  nerve,  or  of  hemorrhage  through  injury 
of  the  thyroid  vessels,  but  it  necessitates  a  new  incision,  and  hence 
another  scar. 


ding   cjMmc.  <*v£r 


*lxc-  cciAfic. 
(vri/     at/. 


Fig.  79. — Ligation  of  the  inferior  thyroid  artery.  Incision  is  made  above  the  clavicle 
in  order  to  penetrate  the  triangle  formed  by  the  sternocleidomastoid,  omohyoid  and  the 
clavicle.  The  thyrocervical  axis  is  then  located  and  the  inferior  thyroid  tied.  Note  the 
close  relation  of  the  phrenic  nerve  to  the  thyrocervical  trunk. 


Hemostasis. — Hemorrhages  were  for  a  long  time  a  feared  complica- 
tion of  goiter  operation.  With  our  present  anatomical  and  technical 
knowledge,  however,  this  complication  can  now  be  avoided  almost 
entirely.  Of  course  there  will  always  be  operations  in  which  hemor- 
rhages, no  matter  what  is  done,  will  be  abundant;  especially  in  Graves' 
disease  where,  because  the  bloodvessels  are  thin  and  friable,  hemorrhage 
is  sometimes  quite  marked  despite  a  good  technic.  There  will  always 
be,  too,  hemorrhages  due  to  some  unexpected  and  unavoidable  accident. 
These  complications,  however,  can  be  reduced  to  a  minimum. 

Hemorrhages  may  be:  1st,  arterial;  2d,  venous;  3d,  parenchy- 
matous. 


LIGA  TIOXS  467 

Despite  unilateral  ligation  of  the  superior  and  inferior  arteries  and 
veins  of  the  thyroid,  we  know  from  our  own  previous  studies  that  hemor- 
rhage may  still  occur  on  account  of  the  bilateral  anastomoses,  and  col- 
lateral circulation  from  the  neighboring  tissues.  Parenchymatous  hemor- 
rhage is,  as  a  rule,  of  little  importance.  In  certain  very  vascular  goiters, 
however,  the  hemorrhage  may  be  so  diffuse  and  so  abundant  that  one 
hardly  knows  where  to  put  a  hemostat.  Furthermore,  the  parenchyma 
and  vessels  may  be  so  friable  that  any  attempt  to  place  a  hemostat  or 
a  ligature  only  results  in  an  increase  of  the  hemorrhage.  The  only,  and 
the  best,  way  to  stop  this  diffuse  parenchymatous  oozing  is  to  use  what 
the  French  authors  call  the  "ligature  en  masse."  This  is  done  by  includ- 
ing in  the  ligature  a  certain  amount  of  glandular  tissue  and  bv  tying 
the  ligature  just  tight  enough  to  stop  the  oozing,  but  not  to  break  the 
glandular  tissue. 

Hemorrhage  can  be  greatly  reduced  if  one  follows  the  following  rule: 
Never  cut  the  glandular  capsule  and  the  parenchyma  unless  previously 
clamped,  and   then  operate  carefully,  anatomically,  and  systematically. 

By  ligating  the  one  or  two  thyroid  arteries  prior  to  undertaking 
resection  of  the  gland  hemorrhage  may  be  reduced  to  a  minimum.  The 
preliminary  ligation  of  both  the  superior  and  inferior  thyroid  arteries, 
prior  to  resecting  the  goiter,  is  not  considered  by  everyone  as  a 
necessary  step  to  the  operation.  In  Kocher's,  De  Quervain's  and 
many  other  surgeons'  work,  ligation  of  both  the  superior  and  inferior 
thyroid  arteries  is  a  part  of  their  technic.  On  the  other  hand, 
Mikulicz,  Kausch,  and  others  do  not  strive  to  do  so.  Kausch,  for 
instance,  ligates  the  superior  thyroid  only:  he  is  never  concerned  with 
the  inferior  thyroid.  I  share  the  same  views,  except  when  I  have  to 
deal  with  thyrotoxic  goiters  in  which  the  diminution  of  the  blood  supply 
of  the  remaining  glandular  portion  is  one  of  the  aims  of  the  operation. 
Otherwise,  in  ordinary  simple  goiters,  I  really  do  not  see  the  necessity 
for  ligating  the  inferior  thyroid  before  removing  the  goiter.  On  the  con- 
trary, I  consider  that  leaving  the  inferior  thyroid  untouched  is  one  of 
the  best  assets  for  the  vitality  of  the  remaining  glandular  portion,  and 
especially  for  its  functional  activity.  It  is  rare  that  hemorrhage-  during 
operation  is  such  that  the  only  means  to  check  it  is  to  add  to  the  liga- 
tion of  the  superior  thyroid  artery,  the  ligation  of  the  inferior  thyroid. 
Another  reason  for  giving  up  the  ligation  of  the  inferior  thyroid  is  to 
avoid  any  chance  of  injuring  the  interior  laryngeal  nerve  and  the  para- 
thyroids, furthermore,  quite  often  the  vitality  ot  the  remaining  por- 
tion of  the  gland  is  already  reduced,  and  consequently  it  it  is  further 
lowered  by  shutting  off  its  main  blood  supply,  it  will  hardly  be  able  to 
take  care  of  the  ligatures'  material,  and  especially  so  if  the  lattei  is  non- 
resorbable,  hence  pus  and  elimination  of  the  threads.    ( )n  the  other  hand, 


468      TECH  NIC  OF  OPERATIOXS   UPON  THE  THYROID  GLAND 

as  a  routine  measure,  I  always  ligate  the  superior  pole  before  starting 
the  resection. 

It  is  scarcely  necessary  to  state,  if  ligation  of  both  superior  and 
inferior  thyroids  is  attempted  by  the  surgeon  as  a  part  of  his  routine 
technic,  since  this  ligation  has  for  its  sole  object  the  reducing  to  a  mini- 
mum of  the  hemorrhage  during  the  surgical  act,  that  it  should  take 
place  before  beginning  the  resection  of  the  gland.  This  again  is  not 
viewed  by  everyone  in  the  same  way:  I  have  often  seen  surgeons  per- 
forming this  ligation  after  the  removal  of  the  goiter  was  terminated. 
At  that  time  of  the  operation,  this  ligation  is,  in  my  judgment,  entirely 
unnecessary,  as  it  presupposes  that  hemorrhage  has  already  been  mas- 
tered. Indeed,  in  the  great  majority  of  cases,  as  soon  as  the  goiter  has 
been  removed,  hemorrhage  diminishes  in  a  surprising  manner:  a  few 
hemostats  here  and  there  and  the  bleeding  is  controlled.  Once  in  a 
great  while,  however,  the  oozing  is  so  profuse  that  it  seems  more  expedi- 
ent to  resort  to  the  ligation  of  the  inferior  thyroid  artery  in  order  to 
check  the  bleeding.  This,  however,  is  rare.  At  any  rate,  if  one  believes 
in  the  necessity  of  ligating  the  inferior  thyroid  artery,  the  only  logical 
moment  to  perform  it  is  before  starting  the  resection  of  the  goiter  itself. 
As  said  before,  exception  can  be  made  for  thyrotoxic  goiters.  In  these 
cases,  if  for  some  reason  ligation  of  the  inferior  thyroid  artery  has  not 
already  been  done,  it  can  then  take  place  after  the  goiter  is  removed. 


Thyroidectomy. 

I  he  low -collar  incision  bein»  performed  and  the  two  skin  Baps  retracted,  the  prethyroid 
musck-s  an-  divided   in  rlu-  middle  line. 


CHAPTER    XLI. 
OPERATIVE  TECHNIC   FOR  THYROIDECTOMY. 

INCISION. 

1.  In  the  greatest  number  of  cases  the  incision  of  choice  is  the  low- 
collar  incision  of  Kocher.  It  is  the  one  which  certainly  gives  the  best 
cosmetic  results  and  when  properly  placed  allows  the  surgeon  to  per- 
form every  step  of  the  operation  without  difficulty.  It  is  slightly 
curved,  its  concavity  being  directed  upwardly;  it  should  be  perfectly 
symmetrical.  The  incision  is  made  one  or  two  centimeters  above  the 
manubrium  sterni.  The  length  varies,  of  course,  with  the  size  of  the 
goiter.  The  fault  too  often  made  by  beginners  is  that  of  a  small  incision. 
In  larger  goiters  the  incision  extends  from  the  middle  of  one  sternocleido- 
mastoid muscle  to  the  other,  or  better  said,  from  one  external  jugular 
vein  to  the  other.  In  the  average  case  it  can  be  made  much  smaller. 
If  local  anesthesia  is  used,  the  incision  must  be  larger  than  with  general 
anesthesia  so  as  to  diminish  the  pain  caused  by  the  necessary  pulling 
upon  the  retractors.  It  is  better  to  give  the  preference  to  a  slightly 
curved  incision  than  to  a  straight  transverse  cut.  In  unusually  large 
goiters  the  esthetic  side  may  have  to  be  disregarded;  the  "Winkelschnitt" 
of  Kocher  or  angular  incision  with  well-rounded  angles  above  the  cricoid 
cartilage  will  then  give  far  better  access  to  the  tumor  than  any  other 
incision.  This  incision,  however,  will  seldom  find  employment  because 
very  large  goiters  are  becoming  more  and  more  rare  every  day,  and 
because,  too,  a  well-arched  collar  incision  will  almost  always  meet  every 
demand. 

Other  incisions  are  sometimes  advocated  as  the  "H,"  "1,"  and 
"U"  forms.  They  only  prove  that  the  surgeon  who  uses  them  is  not 
very  much  concerned  with  the  esthetic  side  of  his  work.  I  hese  inci- 
sions will  soon  have  only  an  historical  interest. 

2.  The  subcutaneous  tissue  and  plat}  sma  are  then  retracted,  the 
upper  Hap  as  high  as  the  thyroid  cartilage,  the  lower  flap  to  the  epi- 
sternal  notch.  (Plate  XVI.)  The  two  median  and  oblique  jugular  veins 
are  clamped  and  cut;  the  two  external  jugular  veins  are  left  uninjured. 

The  upper  and  lower  Haps  are  maintained   retracted  either  by  an  auto- 
matic retractor  or  by  an  assistant. 

3.  A  vertical  incision  extending  from  the  thyroid  cartilage  to  the 
episternal   notch   is   made  in   the   middle-  line  between    the    prethyroid 


470  OPERATIVE  TECH  NIC  FOR   THYROIDECTOMY 

muscles.  (Plate  XVI.)  A  finger  is  then  introduced  under  them  and 
going  up  and  down,  loosens  their  posterior  surface  as  far  up  and  down  as 
possible.  (Plate  XVII.)  The  greater  amount  of  pressure  must  take 
place  anteriorly  against  their  posterior  surface  so  as  to  avoid  injury  of 
the  subjacent  veins. 

4.  For  moderately  sized  and  non-complicated  goiters  the  mere  lat- 
eral retraction  of  the  prethyroid  muscle  affords  sufficient  access  to  the 
field  of  operation.  In  a  great  many  instances,  however,  it  becomes 
necessary  to  cut  them  transversely.  (Plate  XVIII.)  The  point  of  elec- 
tion for  their  section  is  at  their  upper  end;  in  that  way  their  nerve  sup- 
ply is  not  injured  while  the  section  breaks  the  line  of  scar  thus  prevent- 
ing the  muscular  suture  from  becoming  adherent  to  the  cutaneous  one. 
These  muscles  are  clamped  transversely  and  cut  between  parallel  hemo- 
stats,  on  one  or  both  sides  according  to  the  necessity,  and  are  retracted 
laterally  and  downward.  Furthermore,  these  muscles  are  treated  as 
one  structure  technically  throughout  the  operation,  and  are  always 
manipulated  as  one  object;  they  are  not  being  freed  of  their  fascia  cov- 
ering them.  Usually,  however,  the  omohyoid  muscle  does  not  need  to 
be  cut.  The  time  lost  in  liberating,  clamping,  cutting,  retracting,  and 
sewing  up  these  muscles  when  the  operation  is  done  is  practically  not 
worth  mentioning.  At  any  rate,  it  is  more  than  sufficiently  offset  by 
the  ease,  rapidity  and  safety  with  which  the  operation  can  be  done,  and 
by  the  minimum  ot  traumatism  inflicted  upon  the  patient. 

The  sternocleidomastoid  muscle  does  not  need  to  be  incised  at  all. 
Its  lateral  retraction  is  sufficient  to  give  plenty  of  access  to  the  field  of 
operation.  It  may,  however,  become  necessary  in  large  intrathoracic 
goiters  to  cut  temporarily  its  sternoclavicular  insertion.  In  that  case  its 
itwo  ends  must  be  sewed  up  afterward. 

5.  There  is  no  need  to  say  that,  as  the  operation  is  progressing,  every 
bleeding  point  is  at  once  blinded  with  hemostats  which  are  left  in  place 
or  removed  after  immediate  ligature  has  been  made.  In  a  most  general 
way,  but  especially  when  dealing  with  the  gland  itself,  clamping  with 
hemostats  must  always  be  done  before  cutting  and  not  afterward. 

6.  The  surgical  capsule  is  now  open  and  the  glandular  capsule 
exposed.  (Plate  XIX.)  This  step  of  the  operation  is  of  the  utmost 
importance  as  it  affords  the  proper  plane  of  cleavage,  otherwise  the 
surgeon  will  err  in  the  wrong  place  and  the  operation  will  become  very 
difficult.  Two  index  fingers  are  introduced  between  the  surgical  cap- 
sule and  the  goiter  itself  and  conducted  up  and  down  gently  around  the 
goiter  so  as  to  loosen  the  tumor  from  its  connection  with  the  surgical 
capsule.  (Plate  XX.)  In  so  doing  one  often  finds  the  middle  or  accessory 
veins  of  Kocher,  which  in  large  goiters  are  sometimes  markedly  devel- 
oped.    They  are  doubly  clamped  and  cut. 


PLATE    XVII 


*W 


Thyroidectomy. 

he  operator  then   goes  with  the  index  fingers  into    the  musculocapsulai  space,  thus 
loosening  the  prethyroid  muscles  away  from  the  gland. 


INCISION  471 

7.  Now  comes  one  of  the  most  important  steps  of  the  operation,  a 
method  first  introduced  by  Kocher  and  called  dislocation  of  the  goiter. 
One  or  two  fingers  passed  posteriorly  between  the  gland  and  the  surgi- 
cal capsule  lift  the  gland  forward,  the  isthmus  forming,  so  to  speak,  a 
hinge  upon  which  the  lobe  is  swung.  The  surgical  capsule  is  detached 
and  retracted  posteriorly  as  far  as  the  "danger  zone"  (Plate  IX,  Fig.  2), 
but  no  farther,  so  as  to  avoid  coming  in  contact  with  the  parathyroids 
and  inferior  laryngeal  nerve.  Luxation,  too,  should  not  be  pushed  too 
far,  so  as  to  avoid  the  danger  zone.  Occasionally  there  may  be  some 
hemorrhage  from  small  vessels  torn  when  the  gland  is  luxated.  This 
hemorrhage  can  usually  be  easily  controlled. 

In  uncomplicated  cases,  with  not  too  large  a  goiter,  when  the  sur- 
gical capsule  has  not  undergone  any  secondary  inflammation  and  has 
not  become  adherent  to  the  glandular  capsule,  luxation  of  the  goiter 
is  an  easy  matter,  and  of  most  impressive  effect,  especially  when  unsus- 
pected intrathoracic  goiters  are  fished  out.  If,  however,  peristrumitis 
has  taken  place,  as  in  some  cases  of  Basedow's  disease,  strumitis,  and 
malignancy,  the  surgical  capsule  being  fused  with  the  glandular  capsula 
propria,  it  is  no  longer  possible  to  separate  them,  the  good  plane  of  cleav- 
age cannot  be  entered  into.  Under  such  circumstances  the  operation 
becomes  difficult  and  bloody.  It  is  in  such  attempts  to  luxate  the  goiter 
that  alarming  hemorrhages  are  observed,  sometimes  so  intense  that  one 
fears  to  have  injured  the  internal  jugular  or  subclavian  veins.  Under 
such  conditions  luxation  must  often  be  given  up,  and  resection  of  the 
goiter,  after  having  ligated  the  upper  pole  and  possibly  the  inferior 
thyroid  artery,  must  be  undertaken  in  situ.  The  operation  is  more 
difficult  but  is  technically  feasible,  as  shown  by  surgeons  who  never 
luxate,  but  dissect  the  entire  gland  free  from  its  attachments  by  sharp 
dissection  with  scalpel  and  dissecting  forceps,  laying  bare  the  posterior 
capsule.  ( Plate  X,  Fig.  1.)  We  have  seen,  however,  that  such  technic 
is  not  to  be  recommended. 

8.  The  upper  pole  is  freed  from  all  surrounding  structures,  and  the 
left  index  finger  is  placed  between  the  upper  pole  and  the  carotid  sheath 
so  as  to  prevent  injury  to  the  structures  contained.  A  curved,  blunt 
thread  carrier  is  swung  around  the  upper  pole  and  ligation  of  the  thy- 
roid vessels  is  made  (Plate  XXII).  Usually  it  is  easier  to  ligate  the  upper 
pole  so  as  to  bite  off  a  little  of  the  thyroid  tissue.  A  safety  hemostat  is 
placed  outside  of  the  ligature.  This  is  done  for  safety's  sake  so  as  to 
make  doubly  sure  that  no  postoperative  hemorrhage  will  take  place. 
Another  hemostat  is  placed  outside  of  the  Hist,  then  the  upper  pole  is 
severed  with  scissors  between  the  two  hemostats  just  mentioned.  The 
upper  pole  may  be  so  thick  as  to  necessitate  several  hemostats  before 
it  can  be  entirely  severed  from  the  body  oi  the  gland. 


472 


OPERATIVE  TECH  NIC  FOR  THYROIDECTOMY 


9.  If  one  is  a  partisan  of  the  systematic  ligation  of  the  inferior  thy- 
roid artery,  or  if  it  has  become  evident  from  the  nature  of  the  goiter 
that  this  ligation  must  be  undertaken,  it  is  now  the  proper  time  to  per- 
form it.  On  account  of  the  reasons  given  in  the  chapter  concerning 
ligations,  it  must  be  done  far  from  the  danger  zone  at  the  point  of  elec- 
tion, namely,  just  inwardly  of  the  carotid  sheath.     (Plate  XXI.) 


Fig.  80. — 1  he  left  lobe  is  then  resected  in  a  similar  way  as  was  the  right.  The  picture, 
for  clearness'  sake,  shows  that  the  right  lobe  and  isthmus  have  been  separated  from  the 
body  of  the  left  lobe.  In  the  ordinary  technic  of  bilateral  resection  it  is  more  elegant 
to  leave  the  various  portions  of  the  thyroid  in  close  relation  one  with  another  so  as  to 
remove  them  en  bloc. 


10.  Starting  at  the  upper  part  of  the  lobe  and  all  along  the  external 
edge  of  the  gland  (Plate  XXII),  and  progressing  gradually  inwardly 
toward  the  middle  line,  hemostats  are  placed  first  upon  the  glandular 
capsule  and  when  this  has  been  cut,  upon  the  parenchyma  itself  and  so 
on  until  the  entire  portion  which  was  intended  to  be  removed  has  been 
resected  and  until  one  has  reached  the  isthmus.  When  resection  reaches 
the  lower  pole,  one  or  two  small  hemostats  will  take  care  of  the  little 
bundle  of  imae  veins  which  are  always  present.  No  special  effort  is 
made  in  order  to  discover  if  a  thyroid  ima  artery  is  present  or  not:  the 
whole  bundle  of  the  imae  vessels  is  clamped  en  bloc. 


PLATE    XVIII 


Jltyty 


Thyroidectomy. 

W  hen  necessary  the  prethyroid  muscles  are  divided  at   their  superior  ends   after  being 
clamped  between  two  hemostats. 


IXCISIOX  473 

This  mode  of  removing  the  gland  is  known  as  the  transfrontal  resection. 
If  one  wishes  to  resort  to  the  cuneiform  resection,  it  is  done  in  the  way 
and  manner  described  in  Plates  XI  and  XII.  Whatever  method  is 
employed,  great  care  should  be  taken  to  leave  a  thick  enough  portion 
of  glandular  tissue  over  the  danger  zone  so  as  to  protect  the  parathyroids, 
inferior  laryngeal  nerve  (Plate  XXIII)  and  to  safeguard  the  patient 
against  hypothyroidism. 

11.  What  shall  we  do  with  the  isthmus?  Unless  one  has  to  be  very 
economical  with  thyroid  tissue,  the  isthmus  had  better  be  resected. 
If  resection  is  undertaken,  it  is  better  to  start  the  resection  by  its 
lower  border  at  the  junction  of  the  isthmus  and  the  lobe.  When  once 
the  proper  plane  of  cleavage  between  the  isthmus  and  the  trachea  is 
found,  the  operation  goes  on  easily.  Resection  may  be  either  frontal  or 
cuneiform.  If  one  wishes  to  leave  a  thin  strip  of  glandular  tissue  in 
front  of  the  windpipe,  he  may  do  so  (Plate  XXIII);  ordinarily,  however, 
it  is  better  to  lay  the  trachea  bare. 

12.  If  the  operation  must  be  bilateral  the  technic  just  described 
for  the  removal  of  one  lobe  is  applied  in  the  same  way  for  the  other  lobe 
which  is  to  be  removed.  If  the  prelaryngeal  muscles  have  not  been 
severed  before,  they  are  then  retracted,  the  goiter  is  luxated,  its  superior 
pole  and  if  necessary  the  inferior  thyroid  artery  are  ligated  and  resec- 
tion is  undertaken  in  the  way  just  described  (Fig.  80).  Resection  may 
take  place  either  from  the  middle  line  toward  the  outside  as  shown  in 
the  figure  or  vice  versa.  I  prefer  to  resect  from  outside  inside.  Here, 
too,  enough  gland  should  be  left  in  order  to  protect  the  parathyroids, 
the  inferior  laryngeal  nerve,  and  to  form  with  the  portion  left  on  the 
other  side  a  regular  contour  of  the  neck. 

13.  The  pyramidal  process  is  dissected  out  from  below  above  up  to 
its  terminal  point.  One  should  always  be  sure  to  remove  it  all,  other- 
wise compensator)-  hypertrophy  will  take  place  later  on  in  it,  and  give 
rise  to  an  unpleasant  deformity  of  the  neck. 

14.  As  a  general  principle  the  thyroid  gland  should  not  be  removed 
piecemeal.  It  is  far  more  elegant  to  resect  it  in  bloc,  its  two  lobes, 
isthmus  and  pyramidal  process  being  still  in  connection  one  with  the 
other  so  as  to  form  a  whole. 

15.  Fresh,  sterilized  towels  are  put  all  over  the  soiled  ones  and  care- 
ful ligatures  of  whatever  has  been  clamped  are  undertaken.  I  admit 
that  it  is  sometimes  tedious  work,  bur  it  is  the  only  way  to  prevent 
secondary  oozing.  And  even  then  one  cannot  always  guard  against 
that.  Before  removing  the  safety  hemostat  on  the  superior  thyroid 
artery,  another  safety  ligation  should  be  performed  so  as  to  avoid  a 
secondary  arterial  hemorrhage.  Sometimes,  indeed,  the  first  polar  liga- 
tion does  not  hold,  or  the  knot  is  apt  to  slip,  hence  the  necessity  for 
another  safety  ligature. 


474 


OPERATIVE  TECHNIC  FOR  THYROIDECTOMY 


16.  A  careful  exploration  of  the  upper  mediastinum  is  made  for 
thymus  hyperplasia.  If  such  hyperplasia  is  found  to  be  present,  thymec- 
tomy is  performed.  Description  of  the  technic  for  this  operation  will  be 
found  in  the  chapter  on  Thymectomy. 

17.  When  hemostasis  has  been  complete,  and  only  then,  15  minims 
of  a  1 :  1000  adrenalin  solution  are  given  subcutaneously,  in  order  to 
obtain  vasoconstriction  of  the  bloodvessels  and  thus  to  diminish  the 
chances  of  postoperative  oozing.  When  there  is  a  parenchymatous 
oozing  difficult  to  control,  packing  of  the  wound  for  a  minute  or  two 
with  verv  hot  compresses  proves  to  be  very  effective. 


Fig.  81. — The    prethyroid  muscles  are  then  sewed  together  by  a  continuous    running 
suture  which  is  preferable  to  the  interrupted  one  shown  in  the  picture. 


18.  The  prethyroid  muscles  are  then  sewed  up  at  their  upper  end 
and  in  the  middle  line  by  continuous  suture  so  as  to  restore  the  normal 
anatomy  of  the  neck  (Fig.  81).  The  necessity  of  sewing  them  is  not  an 
absolute  one;  probably  more  often  than  is  expected  the  sutures  do  not 
hold;  yet  this  seems  to  have  no  ill  effect  upon  the  cosmetic  aspect  of 
the  neck.  Some  surgeons,  Riedel  for  instance,  do  not  sew  them  up  at 
all.  This  procedure,  however,  is  not  anatomical  and  should  not  be 
recommended. 


PLATE    XX 


W 


VGu 


Thyroidectomy. 

The  surgical  space  is  then  fully  enlarged  and  the  surgical  capsule  is  retracted  as  far 
back  as  necessary,  keeping  in  mind  that  it  should  nor  be  retracted  too  fai  into  the  danger 
zone.     The  glandular  capsule  is  thus  fullv  e  .  >  »s    I. 


PLATE    XXI 


^^ 


a"? 


* 


Thyroidectomy. 

Showing  how  far  back  it  is  safe  to  retract  the  surgical  capsule  and  where  the  ligation 
of  the  inferior  thytoid  artery  should  be  performed  m  order  to  avoid  injury  of  the 
inferior  laryngeal  nerve  and  the  parathyroids. 


OPERATIOX  FOR  INTRATHORACIC  GOITER  475 

19.  In  the  majority  of  cases  drainage  is  not  necessary.  If,  however, 
a  drain  is  to  be  inserted,  it  must  be  done  before  entirely  closing  up  the 
muscular  belt  in  order  to  put  the  end  of  the  drain  in  its  proper  position 
so  as  to  avoid  pressure  on  the  windpipe  or  scratching  of  the  raw  surface 
of  the  thyroid  which  might  cause  hemorrhage.  Following  Kocher's 
example,  I  use  exclusively  a  glass  drain  in  thyroid  surgery.  There  is  no 
need  of  a  special  opening  for  that  drain.  Drainage  through  the  incision 
as  shown  bv  Fig.  82  gives  the  best  results. 


• 


Fig.  82. — Intradermic  suture  is  then  performed.    The  picture  shows  where  the  glass  drain, 

when  used,  should  be  inserted. 

20.  The  platysma  myoides  muscle  is  sewed  up  by  itself  with  a  con- 
tinuous suture.  (Plate  XXV.)  This  is  done  in  order  to  avoid  later  on 
the  spreading  of  the  scar  due  to  traction  of  this  muscle  upon  the  edges  of 
the  wound. 

21.  Intradermic  suture  of  the  skin  is  then  made  (Fig.  82). 

OPERATION    FOR    INTRATHORACIC    GOITER. 

The  operation  is  difficult  and  requires  much  technical  experience 
and  thorough  anatomical  knowledge.  A  low-collar  incision  is  made  in 
the  same  way  and  position  as  for  any  operation  for  goiter.  The  p re- 
thyroid  muscles  are  divided  in  the  middle  line  and  at  both  upper  ends. 

The  most  important  thing  in  such  an  operation  is  to  free  the  cervi- 
cal portion  of  the  goiter  as  completclv  as  possible  from  every  connection 
with  the  other  organs  before  undertaking  the  removal  of  the  goiter; 
consequently  the  upper  pole  must  be  ligated  and  cut.  The  lobe 
to  be  removed  must  be  resected  as  far  down  as  possible,  the  hemostasis 
must  be  complete  before  attempting  to  remove  the  intrathoracic 
portion    of   the  goiter.      When    once   freed   from    its    connection    with 


476  OPERATIVE  TECH  NIC  FOR  THYROIDECTOMY 

the  other  organs  this  cervical  portion  is  used  as  a  tractor  to  pull  the 
intrathoracic  portion  of  the  goiter  upward.  It  is  oftentimes  the  only 
hold  which  we  can  have  on  the  intrathoracic  portion,  consequently, 
every  precaution  should  be  taken  to  preserve  such  connection.  At  this 
stage  of  the  operation,  it  is  often  possible  to  pass  a  finger  or  two  around 
the  lower  pole  of  the  goiter  and  to  dislocate  it  upward.  If  it  is  not  pos- 
sible to  do  so,  then  the  goiter  is  pulled  upward  by  its  cervical  portion, 
slowly,  gradually,  carefully,  each  vessel  coming  in  contact  with  the 
capsule  of  the  goiter,  being  clamped  securely.  It  is  safer  to  ligate  at 
once  the  vessels  in  contact  with  the  lower  portion  of  the  goiter,  because 
otherwise,  if  ligation  is  done  only  after  removal  of  the  goiter,  the  raw 
surface  in  which  the  goiter  was  imbedded  is  aspirated  again  into  the 
thoracic  cavity,  then  ligation  becomes  extremely  difficult  and  may  give 
rise  to  tremendous  hemorrhages.  When  the  intrathoracic  goiter  has 
no  cervical  portion,  and  when  there  is  no  hold  to  pull,  the  goiter  is 
seized  with  the  special  forceps  devised  by  Kocher. 

In  intrathoracic  goiter  surgery,  the  critical  time  of  the  operation  is 
the  moment  when  the  goiter  is  fished  out  of  the  thorax  and  passes  the 
so-called  "critical  space,"  namely,  the  superior  opening  of  the  thorax. 
At  that  time  alarming  hemorrhages  and  choking  of  the  patient  may 
occur.  Blood  sometimes  gushes  up  in  streams  as  from  a  deep  well  and 
may  be  due  to  injury  to  one  of  the  large  veins,  the  internal  jugular,  the 
subclavian,  or  the  innominate.  Suffocation  is  due  to  the  fact  that  the 
goiter  in  passing  the  superior  opening  of  the  thorax  flattens  the  wind- 
pipe. It  is  often  necessary  to  replace  the  goiter  in  the  thorax  in  order  to 
allow  the  patient  to  breathe  again.  This  may  have  to  be  done  several 
times  during  the  surgical  procedure  until  the  goiter  has  passed  the 
"critical  point,"  namely,  the  superior  opening  of  the  thorax. 

The  intrathoracic  goiter  may  be  so  large  that  it  is  impossible  to  pull 
it  through  the  superior  opening  of  the  thorax.  If  we  have  to  deal  with 
a  cyst  the  difficulty  is  easily  turned.  The  cyst  is  punctured  and  its 
contents  aspirated.  If  the  tumor  is  solid  then  the  method  known  as 
"evidement"  or  "morcellement"  used  in  bone  surgery  or  in  fibroid  of 
the  uterus  can  be  successfully  applied  here,  too.  One  finger  goes  firmly 
through  the  tumor  and  shells  it  out  piecemeal.  Then  when  the  goiter 
in  toto  has  been  so  reduced  in  size  as  to  pass  the  superior  opening  of  the 
thorax,  it  is  pulled  out  of  the  thoracic  cavity. 

In  intrathoracic  goiter,  drainage  is  indicated  because  there  is  a  large, 
dead  space  located  at  the  lower  end  of  the  wound,  consequently  this 
cavity  is  bound  to  fill  up  with  blood.  No  packing  should  be  left  in, 
unless  hemorrhage  should  be  abundant  and  cannot  be  controlled. 

Intrathoracic  goiter  surgery  is  one  of  the  most  thrilling  there  is.  If 
one  is  seeking  surgical  emotion,  it  is  surely  in  that  field  that  he  will  find 
what  he  is  looking  for. 


PLATE    XXII 


A^ 


Thyroidectomy. 

Ligation  of  the  upper  pole  is  performed,  the  goiter  is  dislocated  forward  and  a  trans- 
glandular  resection  is  being  made,  starring  along  the  lateral  surface  of  the  goiter  until 
the  lower  pole  is  reached. 


PLATE   XXIII 


Thyroidectomy. 

The  right  lobe  is  then  totally  resected  and  so  is  a  portion  of  the  isthmus.  The  figure 
here  shows  that  a  little  strip  of  the  posterior  portion  of  the  isthmus  has  been  left  in  situ. 
This,  however,  is  not  at  all  necessary.      Usually  the  trachea  is  left  bare. 


TECH  NIC  OF  OPERATIONS  FOR  MALIGNANT  GOITERS        477 

TECHNIC    OF    OPERATIONS    FOR   MALIGNANT    GOITERS. 

For  this  class  of  tumors  it  is  impossible  to  set  down  hard-and-fast 
rules.  The  technic  will  vary  with  the  development  of  the  malignant 
tumor.  In  the  great  majority  of  cases  a  malignant  goiter  develops  from 
a  preexisting  simple  goiter.  For  a  certain  period  of  time  the  growth 
remains  intraglandular,  leaving  the  capsule  entirely  free.  If  one  is 
fortunate  enough  to  meet  with  such  cases  the  technic  will  not  be  more 
difficult  than  in  any  ordinary  goiter.  The  only  thing  to  do  is  to  perform 
a  total  unilateral  or  bilateral  excision  as  the  case  may  be.  Postopera- 
tive hypothyroidism  should  be  a  secondary  consideration,  since  we 
know  that  cachexia  strumipriva  occurs  only  once  out  of  two  or  three 
cases  of  complete  thyroidectomy.  At  any  rate  we  have  not  the  choice. 
If  symptoms  of  hypothyroidism  develop,  thyroid  opotherapy  will 
remedy  such  complications  Tetany  may  develop,  too,  but  can  be 
successfully  met  with  our  modern  methods  of  treatment. 

Unfortunately,  in  the  greatest  number  of  instances  the  surgeon  sees 
such  cases  only  when  the  growth  has  already  invaded  the  capsule  and 
the  neighboring  tissues,  as  the  trachea,  esophagus,  large  bloodvessels, 
and  the  nerves.  In  such  conditions  complete  removal  of  the  tumor  is 
impossible:  operation,  if  at  all  performed,  can  be  only  palliative. 


CHAPTER   XLII. 

OPERATIVE  ACCIDENTS. 

Lesions  of  the  Nerves. — Injuries  to  the  inferior  laryngeal  nerves  were 
extremely  frequent  when  total  thyroidectomies  were  performed  and  when 
the  technic  of  goiter  operation  had  not  reached  its  present  state  of 
development.  Billroth,  for  instance,  in  71  extirpations  of  goiter  had  23 
partial  or  complete  paralyses  of  the  larynx.  In  1885  Jenkowsky  in  100 
goiter  operations  observed  paralysis  of  the  vocal  cords  14  times.  Today 
these  accidents  are  rare  and  with  good  technic  should  not  occur. 

Injury  to  the  inferior  laryngeal  nerve  is  most  liable  to  occur: 

1.  When  the  inferior  thyroid  artery  is  ligated;  hence  the  indication 
to  perform  the  operation  far  from  the  thyroid,  namely,  on  the  inner 
border  of  the  carotid  sheath. 

2.  When  resecting  the  gland;  hence  the  indication  to  leave  a  thick 
layer  of  glandular  tissue  in  connection  with  the  posterior  capsule. 

If  these  two  requirements  are  observed  there  should  be  no  direct 
injury  to  the  inferior  laryngeal  nerves.  It  must  be  said,  however,  that 
a  temporary,  and  even  a  permanent,  paralysis  of  the  vocal  cords  has 
been  observed  even  when  no  direct  injury  whatsoever  to  the  inferior 
laryngeal  nerve  was  done.  Wolfler  found  12  of  such  cases.  Paralysis 
in  such  cases  is  due,  either  to  formation  of  connective  tissue  around  the 
inferior  laryngeal  nerve,  or  is  associated  with  a  previous  paretic  condi- 
tion of  the  vocal  cords,  caused  by  the  goiter  itself.  Hence  the  indica- 
tion never  to  forget  to  make  a  laryngoscopic  examination  of  patients 
affected  with  goiter,  as  such  a  systematic  examination  will  not  only 
reveal  unsuspected  paretic  or  paralytic  conditions  of  the  cords,  but  will 
also  be  a  protection  to  the  surgeon  since  it  enables  him  to  warn  the  patient 
that  a  hoarseness  or  even  temporary  loss  of  voice  may  follow  the 
operation. 

Bilateral  injury  of  the  inferior  laryngeal  nerves  is  not  common.  In 
1890  Wolfler  reported  6  of  such  cases.  Four  times  death  occurred  from 
aspirative  pneumonia. 

Injury  to  one  of  the  inferior  laryngeal  nerves  is  of  good  prognosis. 
If  the  nerve  has  been  accidentally  resected  or  pinched  in  a  ligature,  its 
continuity  is  never  reestablished,  although  the  patient  will  in  time 
recover  his  voice  on  account  of  the  compensatory  swinging  over  of  the 
other  cord.  Phonation  will  in  time  become  so  improved  that  the  patient 
is  unaware  of  any  change.    Leischner  collected  67  cases  of  postoperative 


Thyroiclee  corny. 

\  u\v  of  the  field  of  operation  after  bilateral  resection  has  been  performed.     As  stated 
before,  a  small  strip  of  glandular  tissue  representin»  the  isthmus  is  usually  not  present. 


PLATE    XXV 


11  f^'V 


Thyroidectomy. 
The  platysma  myoides  muscle  is  sewed  up  by  itself  by  a  continuous 


running  suture. 


SUFFOCATION  AND  COLLAPSE  OF  THE  TRACHEA  479 

troubles  of  varying  degree  due  to  the  injuries  mentioned.  In  4  cases 
there  was  paralysis  of  both  cords;  6  cases  of  unilateral  paralysis;  35 
cases  of  unilateral  paresis;  19  cases  of  slight  unilateral  paresis;  and  3 
cases  of  slight  bilateral  paresis.  The  final  results  in  these  cases,  as  to 
the  return  of  the  vocal  function,  were  as  follows:  Of  the  4  cases  of  bilat- 
eral paralysis,  2  patients  regained  normal  voice  and  2  remained  very 
hoarse.  Of  the  6  cases  of  unilateral  paralysis,  3  patients  regained  their 
voices,  2  remained  hoarse  and  1  was  hoarse  occasionally.  Of  the  19 
cases  of  unilateral  paresis  of  slight  degree,  17  regained  their  voices  and 
2  remained  hoarse.  Of  the  3  cases  of  bilateral  paresis,  the  voices  became 
normal.  Of  the  35  cases  of  unilateral  paresis,  22  regained  their  voices, 
2  remained  hoarse,  and  4  were  hoarse  occasionally. 

Many  authors  have  reported  cases  of  vocal  disturbances  existing 
before  the  operation  which  disappeared  very  soon  after  goiter  had  been 
removed.  In  such  conditions  the  disturbances  are  caused  by  a  simple 
irritation  of  the  recurrent  nerve  on  account  of  pressure.  As  soon  as  the 
goiter  has  been  removed,  pressure  ceases,  hence  restitutio  ad  integrum 
of  the  nervous  function.  In  other  conditions  the  vocal  disturbances  are 
caused  by  a  congestive  condition  of  the  larynx,  caused  by  pressure  from 
the  goiter  on  the  laryngotracheal  tube.  There,  again,  as  soon  as  the 
goiter  is  removed,  compression  disturbances  and  congestion  cease,  while 
the  vocal  cords  return  to  their  normal  condition,  and  consequently  to 
their  normal  function. 

Injuries  of  the  superior  laryngeal  nerve  are  infrequent.  Injuries  of 
the  phrenic  and  sympathetic  nerves  may  occur  only  in  malignant  goi- 
ters. Injury  of  the  hypoglossus  may  accidentally  occur  in  large  goiters 
extending  high  up  into  the  submaxillary  region.  Injury  to  the  vagus 
nerve  occurs  frequently  during  removal  of  malignant  goiters.  Not  so 
uncommonly  the  nerve  must  be  cut  away  with  the  tumor.  Usually  the 
division  or  resection  of  the  vagus  is  harmless.  Its  irritation,  however, 
through  stretching  or  pinching  with  a  liemostat,  is  far  more  serious, 
since  it  may  lead  to  diminished  cardiac  action,  lowered  blood-pressure, 
dyspnea,  and  even  collapse  and  death. 

Suffocation  and  Collapse  of  the  Trachea.  One  of  the  most  dramatic 
accidents  which  may  occur  during  goiter  operation  is  suffocation.  It  is 
found  mostly  in  connection  with  partially  or  totally  intrathoracic  goi- 
ters. It  is  due  to  occlusion  of  the  windpipe,  either  because  the  trachea 
is  compressed  by  the  tumor  when  passing  the  superior  opening  oi  the 
thorax,  or  because  the  displacement  and  compression  of  the  windpipe 
arc  exaggerated  during  the  operative  maneuvers.  And  strange  as  it 
may  stem,  suffocation  mav  occur  even  after  the  goiter  has  been  entirely 
removed.  At  first  this  seems  paradoxical.  We  have  seen,  however, 
that  in  long-standing  goiters   pressure   causes  atrophy  <>l   the  tracheal 


480  OPERATIVE  ACCIDENTS 

walls;  they  consequently  become  soft  and  pliable.  While  the  goiter  is 
present  it  acts  as  a  splint  and  supports  the  weakened  portion  of  the 
trachea.  But  suppose  we  remove  the  goiter.  No  longer  reinforced  by 
the  goiter  and  having  lost  their  normal  elasticity  the  walls  of  the  trachea 
are  sucked  in  with  each  inspiration.  The  more  violent  the  efforts  at 
each  inspiration,  the  more  complete  will  be  the  occlusion,  because  the 
atrophied  walls  are  drawn  into  the  tracheal  lumen  like  a  valve,  and  as 
mechanical  obstruction  of  the  windpipe  is  always  accompanied  by 
catarrh  and  edema  of  the  laryngeal  and  tracheal  mucous  membrane,  the 
lumen  of  the  trachea  available  for  respiration  consequently  becomes 
utterly  insufficient.  If  the  operation  is  performed  under  local  anes- 
thesia, the  patient  will  soon  protest  in  such  a  way  that  the  surgeon  is 
bound  to  know  that  something  is  radically  wrong.  Even  if  general 
anesthesia  is  used,  and  if  the  accident  happens  during  the  operation, 
the  surgeon  will  soon  locate  the  trouble.  But  if  the  accident  happens 
after  the  operation  is  over,  if  the  surgeon  has  not  noticed  during 
operation  the  condition  of  the  trachea,  and  if  he  is  not  aware 
that  such  an  accident  is  possible,  he  will  think  that  he  is  confronted 
with  a  case  of  cardiac  collapse,  of  thymic  hyperplasia,  or  will  incrimi- 
nate the  anesthetic.  In  the  meantime  the  life  of  the  patient  will  be  fast 
slipping  away. 

If  suffocation  takes  place  during  the  passage  of  the  goiter  through 
the  superior  opening  of  the  thorax  during  the  act  of  fishing  it  out  of  the 
mediastinal  space,  and  if  luxation  cannot  take  place  very  quickly, 
as  already  stated,  it  is  better  to  push  the  goiter  back  again  into  its 
former  place  in  order  to  relieve  pressure.  This  may  have  to  be  done 
several  times  until  the  goiter  has  been  sufficiently  loosened  from  the 
surrounding  structures  and  removed.  In  some  other  instances  luxation 
must,  on  the  contrary,  be  completed  very  quickly,  as  suffocation  will 
cease  only  when  this  luxation  is  complete. 

If  suffocation  is  due  to  an  aspirative  collapse  of  the  tracheal  walls 
on  account  of  their  atrophy,  the  case  is  a  little  more  difficult  to  handle. 
The  ordinary  tubes  for  larynx  intubation  are  of  no  value  because  the 
obstruction  lies  lower  than  these  tubes  can  reach.  Catheterism  of  the 
trachea  with  catheters  used  for  intratracheal  insufflation  are  the  only 
ones  which  can  be  useful.  They  may  be  left  in  situ  until  the  walls  of 
the  trachea  have  become  self-supporting. 

The  best  plan,  however,  which  has  proved  successful  with  other 
surgeons  and  myself  is  to  pass  at  the  time  of  the  operation  one  or  two 
threads  through  the  collapsing  walls  and  to  suture  them  to  the  muscular 
belt,  with  just  enough  tension  to  maintain  the  collapsing  walls  far  apart, 
but  not  so  as  to  tear  the  suture  through.  The  head  should  then  be 
immobilized  so  as  to  set  the  cervical  muscles  at  rest.     The  threads  will 


AIR  EMBOLISM  481 

hold  just  long  enough  to  allow  the  trachea  to  become  adherent  in  its 
new  position  to  the  neighboring  tissues,  and  consequently  to  prevent 
any  further  collapse. 

As  a  means  of  last  resort  there  remains  tracheotomy. 

It  is  really  impossible  to  set  down  hard-and-set  rules  for  each  case. 
The  surgeon  himself  must  decide  at  the  time  what  is  really  best  to  do 
in  each  given  condition.  In  that  critical  moment  the  decision,  experi- 
ence and  skill  of  the  surgeon  will  be  the  best  assets  to  guard  the  patient 
against  death. 

Injury  to  the  Trachea,  Esophagus  and  Pleura. — In  non-malignant 
goiters,  accidental  injury  of  the  trachea  and  esophagus  practically  never 
occurs.  If  it  does,  it  must  be  charged  to  an  error  in  technic.  In  malig- 
nant goiters,  however,  which  have  grown  adherent  to  the  esophagus  and 
trachea,  partial  resection  of  the  latter  organs  may  have  to  be  deliber- 
ately undertaken.     In  strumitis  such  a  resection  is  not  warranted. 

Injun'  to  the  pleural  membrane  is  very  rare  and  occurs  in  conjunc- 
tion with  removal  of  intrathoracic  goiters. 

Tracheotomy.  While  starting  out  to  operate  a  goiter  a  surgeon  may 
be  called  upon  to  perform  a  tracheotomy  in  patients  choking  on  account 
of  pressure  from  goiter.  In  order  to  be  successful  the  operation  must 
be  methodical,  and  at  the  same  time  very  rapidly  done.  It  is  not  always 
an  easy  matter  to  open  the  trachea  while  a  patient  is  choking  to  death, 
while  there  is  an  intense  congestion  of  the  entire  cervical  region,  while  a 
large  goiter  prevents  getting  at  the  windpipe  quickly,  and  while  the 
trachea  is  so  displaced  and  compressed  that  the  anatomical  landmarks 
are  completely  disturbed.  And  indeed  it  is  not  enough  to  open  the  wind- 
pipe, but  the  cannula  introduced  into  the  trachea  must  be  long  enough  to 
pass  the  stenosis.  This  is  not  always  the  case,  as  compression  may  take 
place  low  down  in  the  thorax.  Our  ordinary  cannulas  in  such  cases  are 
not  always  long  enough  to  reach  the  stenotic  point,  hence  the  necessity 
of  always  having  longer  cannulas  provided  for  emergencies.  Such  have 
been  devised  by  several  authors  especially  Verneuil,  K6mg,  Poncet,  etc. 

Air  Embolism.  One  of  the  greatest  dangers  connected  with  injury  of 
the  venous  trunks  in  goiter  operations  is  air  embolism.  In  ordinary  condi- 
tions the  thinness  of  the  walls  of  the  veins  and  their  natural  tendency 
to  collapse  makes  air  embolism  quite  unlikely.  However,  in  goiters 
complicated  with  strumitis  or  malignant  degeneration,  air  embolism  is 
very  apt  to  occur,  because  the  veins  being  adherent  cannot  collapse. 
The  only  time  that  I  have  met  with  such  an  accident  was  while  removing 
a  malignant  goiter.  Here  the  subclavian  was  adherent  to  the  tumor 
and  was  inadvertently  injured.  Before  I  succeeded  in  locating  tht- 
bleeding  vessel  and  clamping  it,  enough  air  had  been  aspirated  into  the 
circulatory  system  so  that  death  followed  two  days  after  without  the 
patient  having  regained  consciousness. 
31 


CHAPTER    XLIII 


SYMPATHECTOMY. 


Thinking  that  Graves'  disease  was  due  to  a  neurosis  of  the  sympa- 
thetic system,  Jaboulay  sought  to  cure  it  by  performing  sympathec- 
tomy. The  first  operation  was  done  by  him  on  February  8,  1896. 
Jonnesco  and  Abadie  at  once  adopted  the  same  method  of  treat- 
ment and  two  years  later,  Jonnesco  was  able  to  report  10  cases  of  sympa- 
thectomy with  6  complete  cures,  4  improvements,  and  no  deaths.  From 
that  time  on  the  operation  was  performed  by  a  great  number  of  surgeons 
until  1900  when  it  gradually  fell  into  disrepute.  In  1899  Garre  per- 
formed a  bilateral  resection  of  the  sympathetic  nerve  in  a  patient  who 
had  already  undergone  thyroidectomy.  In  this  case  the  exophthalmos 
was  so  marked  that  ulceration  of  the  cornea  followed,  the  resection  of 
the  sympathetic  remained  without  any  effect.  In  1902  Ballacescu  and 
Jonnesco  advocated  a  complete  resection  of  the  cervical  sympathetic 
nerve  including  the  superior,  middle  and  inferior  ganglia.  In  1908 
Kocher  had  intervened  only  three  times  on  the  cervical  sympathetic 
with  1  success,  1  failure  and  1  death.  Landstrom  combined  in  one 
case  thyroidectomy  with  sympathectomy  and  obtained  a  complete 
cure.  In  England  and  America  the  same  disregard  for  the  operation  is 
observed.  Curtis  performed  it  7  times  and  gave  it  up  as  a  dangerous 
operation  because  he  had  3  deaths  out  of  the  7  cases.  In  1910  Jonnesco 
reported  30  operations  for  Basedow's  disease  without  death.  Twice  he 
performed  a  resection  of  the  superior  and  middle  ganglia  and  16  times 
a  cervicothoracic  sympathectomy,  thus  resecting  entirely  the  cervical 
trunk  including  the  superior,  middle,  and  inferior  ganglia.  For  the 
time  being,  only  two  surgeons,  Jaboulay  and  Jonnesco,  have  remained 
true  to  that  method  of  operation. 

The  most  complete  statistics  we  have  on  that  subject  are  those  given 
by  A.  Charlier;  they  refer  to  the  material  taken  from  the  clinic  of 
Jaboulay  from  1896  to  1910.  Jaboulay  performed  sympathectomy  in 
31  cases,  23  women  and  8  men.  In  1  case  bilateral  elongation  only  of  the 
nerve  was  performed.  In  9  cases  the  mere  division  of  the  nerve,  namely, 
sympatheticotomy  was  performed,  twice  unilaterally  and  7  times  bilater- 
ally. In  the  remaining  21  cases,  resection,  namely,  partial  sympathectomy 
including  the  resection  of  the  superior  ganglion  was  performed;  4  times 
the  operation  was  unilateral  and  17  times  bilateral;  twice  only  the 
removal  of  the  middle  ganglion  was  added  to  it.  Four  of  these  cases 
had  already  undergone  thyroidectomy  without  results;  3  of  these  sym- 


IMMEDIATE  RESULTS  OF   THE  OPERATION  483 

pathectomized  cases  had  to  undergo  a  subsequent  thyroidectomy  on 
account  of  failure  of  the  sympathectomy  to  bring  about  relief.  Out  of 
the  31  cases  of  Jaboulay's  6  died,  thus  giving  a  death-rate  of  19.35  per 
cent.  One  patient  died  from  thymus  hyperplasia.  The  immediate  post- 
operative course,  according  to  Charlier,  was,  as  a  rule,  very  benign — 
some  fever,  some  dysphagia,  were  about  all.  There  was  often,  however, 
a  complication  which  seemed  to  threaten  the  life  of  the  patient,  namely, 
bronchopneumonia.  Four  out  of  the  6  cases  of  Jaboulay's  statistics 
died  on  account  ot  pulmonary  complications.  A  very  severe  hyper- 
thyroidism may  follow  the  operation,  as  in  Duret's  experience. 

Pathology. — The  morphological  nature  of  the  sympathetic  is  exceed- 
ingly variable;  it  is  consequently  difficult  to  know  what  is  pathological 
or  what  is  not.  In  some  instances  the  ganglia,  as  observed  by  Herbert, 
Eulenberg,  Guttman,  Reith,  Moore,  especially  the  superior,  are  materi- 
ally increased  in  size,  congested  and  red.  Jaboulav  noticed  very  fre- 
quently an  increased  vascularization  of  the  whole  sympathetic.  The 
microscopic  examination,  made  by  various  authors,  of  the  sympa- 
thetic ganglia  and  cord  taken  on  the  whole  does  not  reveal  any  micro- 
scopic changes.  On  the  other  hand,  L.  B.  Wilson  found  definite 
histological  changes  in  the  cells  of  the  cervical  sympathetic  ganglia  in 
exophthalmic  goiter.  These  histological  changes  consisted  of  various 
stages  of  degeneration,  namely,  (1)  hyperchromatization,  (2)  hyperpig- 
mentation,  (3)  chromatolvsis,  and  (4)  atrophy,  or  (5)  granular  degenera- 
tion of  the  nerve  cells. 

So  far  as  could  be  determined  from  the  small  number  of  observa- 
tions, the  pathological  changes  in  the  cervical  sympathetic  ganglia  were 
parallel  to  the  stage  and  intensity  of  the  symptoms  of  hyperthyroidism 
and  to  the  hyperplastic  and  regressive  changes  in  the  thyroid. 

The  fact  that  the  exophthalmos  retrocedes  so  quickly  has  been 
interpreted  as  due  to  the  vasoconstriction  of  the  vessels  of  the 
orbit.  I  his,  however,  cannot  be  the  case  because  we  know  that  sec- 
tion of  the  sympathetic  causes  a  vasodilatation,  as  is  shown  by  the  con- 
gestion of  the  veins  of  the  conjunctiva  and  the  retina,  caused  by  the 
vasodilatation  of  the  retrobulbar  vessels.  Consequently,  if  the  inter- 
pretation given  were  correct,  instead  of  a  diminished,  we  should  have  an 
increased  exophthalmos. 

Immediate  Results  of  the  Operation.  One  of  the  most  constant  and 
most  noticeable  results  is  the  diminution  or  disappearance  of  exoph- 
thalmos. I  his  feature  is  sometimes  noticeable  on  the  operating  table. 
It  is  very  likely  due  to  the  paralysis  of  the  unstriped  musculature  of 
the  orbit,  especially  Landstrom's  muscle.  At  the  same  time  there  is 
a  marked  diminution  of  the  widening  of  the  palpebral  fissure-  due  to 
the  paralysis  of  Midler's  muscle;  the  pupils  become  more  contracted. 
An  exaggerated  secretion  of  the  lachrymal  glands  lasting  only  a   few 


484  5  ]  MPA  THECTOM V 

days  is  sometimes  seen.  Jaboulay  has  observed  that  a  sympathectomy 
has  a  peculiar  and  remarkable  influence  on  certain  cases  of  near-sighted- 
ness. It  causes  a  remarkable  improvement  of  vision,  the  distant  vision 
especially  showing  such  benefit.  Jaboulay  believes  that  this  is  due  to 
the  fact  that  the  eyes  sink  back  into  the  orbital  cavity  and  become 
smaller  as  the  result  of  sympathectomy.  He  bases  his  contention  upon 
the  fact  that  the  more  one  is  near-sighted,  the  larger  and  more  protruding 
are  the  eyes. 

Everyone  seems  to  agree  that  when  sympathectomy  is  successful  the 
subjective  symptoms  of  the  patient  show  a  considerable  improvement. 
He  becomes  more  quiet,  less  impressionable,  less  agitated,  tremor  dimin- 
ishes; tachycardia,  however,  is  little  influenced  or  not  at  all,  and  the 
same  is  true  for  the  goiter. 

In  conclusion  it  may  be  said  that  the  results  obtained  from  sympa- 
thectomy when  present  are  very  immediate.  The  ocular  symptoms  are 
the  ones  most  happily  influenced  by  the  operation;  the  others  such  as 
nervousness,  tachycardia,  and  goiter,  are  problematical. 

Remote  Results. — In  going  over  the  cases  operated  bv  Jaboulav  as 
far  back  as  twelve  and  fourteen  years,  A.  Charlier  was  able  to  find  that  a 
number  of  his  patients  had  been  cured  completely.  He  was  able  to  retrace 
1 8  out  of  the  31  cases  operated  by  Jaboulay  from  four  to  fourteen  years  be- 
fore. Three  of  them  were  completely  cured,  9  of  them  were  so  ameliorated 
that  the  subjective  cure  was  a  complete  one,  the  objective  cure,  how- 
ever, being  incomplete;  the  6  remaining  cases  were  doubtful.  All  these 
patients  experienced  considerable  benefit  to  their  nervous  symptoms; 
in  all  exophthalmos  had  either  disappeared  or  subsided;  vision  was 
improved  and  no  trophic  disturbances  of  any  sort  followed  as  the  result 
of  sympathectomy.  The  cardiac  disturbances  and  goiter  were  the  symp- 
toms less  influenced  and  the  ones  in  which  the  improvement  showed 
less. 

The  impression  one  gains  in  going  over  the  literature  on  this  subject 
is  that  failures  and  relapses  seem  to  be  quite  frequent  with  this  method. 

Choice  of  Operation. — The  results  observed  by  Jaboulav  seem  to  be 
more  or  less  the  same  no  matter  whether  sympathectomy,  or  svmpa- 
theticotomy,  or  simple  elongation  of  the  sympathetic  has  been  done. 
This  is  a  very  important  point  to  note  since  it  follows  that  extensive 
operations  upon  the  sympathetic,  as  for  instance,  complete  removal  of 
its  cervical  portion  including  the  superior,  middle  and  inferior  ganglia, 
as  advocated  by  Jonnesco,  are  not  only  most  laborious,  most  difficult, 
and  most  prolonged  operations,  but  would  also  appear  to  be  unneces- 
sary surgical  risks.  The  simple  unilateral  partial  sympathectomy  gives 
sometimes  about  as  good  results  as  the  bilateral,  yet  the  maximum  of 
effect  is  obtained  solely  by  bilateral  intervention.  The  age  and  sex  of 
the  patients  seem  to  be  of  no  particular  importance  since  the  results  are 


PLATE    XXVI 


Infernal  jugular  vein 


Superior  tKyroid  vesse 


Sympathectomy. 


*     ■ 


- 


SURGICAL  TECHXIC  FOR  SYMPATHECTOMY  485 

the  same  for  young  or  old,  for  men  or  women.  The  operation  upon 
the  sympathetic  is  especially  successful  in  cases  of  Basedow's  disease 
where  exophthalmos  is  very  marked  and  where  little  or  no  goiter  is 
present.  Here,  too,  the  sooner  the  operation  is  performed,  the  better 
the  results  will  be. 

Surgical  Technic  for  Sympathectomy. — The  preparatory  treatment  of 
the  patient  for  operation  is  absolutely  the  same  as  for  any  other  thyroid 
operation.  When  once  it  is  admitted  that  an  extensive  operation  involv- 
ing the  entire  cervicothoracic  trunk  of  the  sympathetic  does  not  give 
better  results  than  simple  partial  resection,  then  this  latter  operation 
must  be  considered  as  the  method  of  choice. 

The  location  of  the  incision  will  depend  upon  the  following  condi- 
tions: if  sympathectomy  is  going  to  be  the  only  surgical  act,  and  is  not 
to  be  combined  at  the  time  of  the  operation  or  later  with  thyroidectomy, 
then  the  incision  is  better  made  parallel  to  the  anterior  border  of  the 
sternocleidomastoid  muscle,  the  middle  of  the  incision  being  located 
at  about  the  level  of  the  upper  border  of  the  thyroid  cartilage.  (Plate 
XXVI.)  If,  however,  sympathectomy  must  be  combined  either  at  the 
time  of  the  operation  with  thyroidectomy  or  thymectomy,  then  the 
incision  had  better  be  the  usual  transverse  or  low-collar  one,  adopted 
for  thyroidectomy.  Through  the  latter  incision  it  is  possible,  not  only 
to  remove  the  thyroid  and  the  thymus,  but  also  to  ligate  the  inferior 
thyroid  artery  and  to  remove  the  sympathetic  which  lies,  as  a  rule, 
just  behind  the  inferior  thyroid.  If  the  lateral  incision  is  made,  ligation 
of  the  upper  pole  (Plate  XXVI)  can  be  made  at  the  same  time  as 
shown  by  Mayo. 

The  sternocleidomastoid  muscle  is  reclined  laterally.  The  same  is 
done  with  the  carotid  sheath  after,  however,  having  located  the  vagus 
nerve.  The  thyroid  gland  and  the  thyroid  cartilage  are  reclined 
inwardly.      (Plate  XXVI.) 

When  trying  to  locate  the  sympathetic  it  is  well  to  remember  that  it 
lies  just  behind  the  carotid  sheath  on  the  prevertebral  fascia  covering 
the  rectus  capitis  anticus  major  and  the  longus  colli  muscles  about 
one-halt  centimeter  inwardly  of  the  transverse  processus  of  the  cervical 
vertebrae.  Chassaignac's  tubercle,  or  transverse  process  of  the  sixth 
cervical  vertebra,  is  a  good  landmark  when  locating  the  sympathetic 
and  its  middle  ganglion  in  the  region  of  the  inferior  thyroid.  The 
carotid  sheath  does  not  fuse  intimately  with  the  cellular  atmosphere 
sin  rounding  the  sympathetic,  hence  the  possibility  of  reclining  the 
carotid  sheath  laterally,  thus  leaving  the  sympathetic  exposed  and  in  inti- 
mate contact  with  the  prevertebral  fascia.  It  sometimes  happens  that 
the  sympathetic  trunk  is  not  found.  In  that  case  it  is  well  to  release  the 
carotid  sheath  from  the  retractor, as  it  sometimes  happens  that  in  Helm- 
ing the  vascular  sheath  the  sympathetic  follows.      I  his  is  not  frequent, 


486 


SYMPATHECTOMY 


however.  The  operation  is  sometimes  made  more  difficult  by  the  pres- 
ence of  hyperplastic  lymph  nodes  more  or  less  adherent  to  the  carotid 
sheath;  in  that  case  the  lymph  nodes  must  be  removed  before  access  can 
be  had  to  the  sympathetic. 


Superioi- 
cervicaL 


Kiddle  cervicci!  ganglion 


Inferior  cervical  ganglion 
In\ev\ov  "fWoid.  arter-y_ 


Fig.  83. — Relation  of  the  sympathetic  to  the  surrounding  structures.  Note  the 
inferior  thyroid  artery  passing  between  some  of  the  sympathetic  fillets.  Note,  too,  the 
position  of  the  middle  cervical  ganglion. 


As  a  rule  the  sympathetic  lies  directly  behind  and  slightly  inward 
from  the  vagus  nerve  (Fig.  83).  It  must  be,  as  already  said,  an  absolute 
rule  never  to  resect  the  sympathetic  without  first  having  exposed,  or  at 
least  located,  the  vagus  nerve.  When  once  located,  the  sympathetic  is 
followed  as  far  up  and  down  as  possible,  and  then  resected.  If  the  superior 
and  middle  ganglion,  or  one  of  them  only,  can  be  resected  at  the  same 
time,  that  should  be  done. 

The  removal  of  the  inferior  sympathetic  ganglion  is  a  delicate  opera- 
tion, inasmuch  as  it  lies  in  the  upper  part  of  the  mediastinal  space,  is  of 
very  difficult  access,  and  is  surrounded  by  a  number  of  very  important 
organs. 


CHAPTER    XLIV. 

CANTHORRAPHY. 

In  some  patients  despite  thyroidectomy  and  sympathectomy,  exoph- 
thalmos remains  unaffected  and  becomes  a  source  of  trouble  and  great 
annoyance  to  the  patient.  Such  patients  are  sometimes  greatly  bene- 
fited by  a  canthorraphy.  This  consists  in  scalping  the  edge  of  both  lids 
from  a  quarter  to  a  third  of  an  inch  at  the  outer  canthus  and  sewing 
the  denuded  marginal  portions  of  the  lids. 


CHAPTER    XLV. 

BOILING-WATER   INJECTIONS. 

Boiling-water  injections  into  the  thyroid  gland  for  hyperthyroidism 
have  been  devised  lately  by  M.  F.  Porter.  This  method  is  based  upon 
the  old  principle  which  is  at  the  base  of  any  injection  method,  namely, 
to  destroy  a  portion  of  the  parenchyma.  We  have  seen  in  the  chapter 
devoted  to  injection  methods  for  simple  goiter,  that  almost  any  medica- 
ment has  been  used.  M.  F.  Porter  uses  boiling  water,  which  is  less 
irritative  and  just  as  effective  as  any  other  means  for  bringing  about 
degeneration  of  the  parenchyma  and  the  formation  of  connective  tissue 
instead.  It  has  the  same  advantages  and  disadvantages  of  all  the  injec- 
tion methods.  It  is  of  simple  application  and  reduces  the  surgical  shock 
to  a  minimum,  yet  Babcock  had  I  death  from  acute  hyperthyroidism, 
and  Mavo,  2  deaths.  The  method  is  not  devoid  of  danger  because  injec- 
tion may  be  made  erroneously  intravenous.  As  sloughing  and  subsequent 
infection  have  occasionally  been  the  results  of  injection  methods,  it 
is  reasonable  to  assume  that  this  may  be  the  same  for  the  boiling-water 
method,  although  accidents  have  not  yet  happened  in  Porter's  experi- 
ence. It  is  difficult  to  judge  how  much  parenchyma  is  being  destroyed, 
and  the  method  has  furthermore  the  disadvantage  of  converting  tin- 
thyroid  into  a  more  or  less  great  mass  of  connective  tissue,  thus  exposing 
the  patient  later  on  to  respiratory  disturbances  on  account  of  compres- 
sion of  the  trachea.  I  can  recall  a  case  of  parenchymatous  goiter  which 
had  been  treated  by  medicamentous  injections,  and  in  winch  just  such 
a  complication  occurred.  The  patient  finally  had  to  be  operated  in 
order  to  relieve  the  pressure  symptoms. 

The  method,  however,  lias  its  clear  indications  and  ma\   be  oi  gnat 


488  BOILING-WATER  INJECTIONS 

value  in  preparing  for  subsequent  operations,  patients  who,  for  the 
time  being,  are  too  bad  surgical  risks.  Personally,  however,  I  have 
never  used  it.  In  Porter's  and  Babcock's  judgments,  this  simple  opera- 
tion can  very  well  be  compared  to  ligation  so  far  as  its  efficacy  is 
concerned.  The  technic  of  the  operation  as  given  by  Porter  is  as  follows. 
Technic. — "An  all-glass  syringe  of  10  c.c.  to  20  c.c.  capacity  is 
best.  The  greater  the  capacity  of  the  syringe  the  longer  the  heat  of 
the  water  is  retained.  The  needle  should  be  long,  flexible,  and  rather 
fine.  The  syringe  is  boiled  with  the  water  over  a  gas  or  alcohol  flame 
by  the  side  of  the  table  or  bed  on  which  the  patient  is  lying.  After 
proper  cleansing  the  areas  to  be  injected  are  infiltrated  with  1  per 
cent,  novocain.  The  filled  syringe  is  removed  from  the  water,  which  is 
actually  boiling,  and  the  injection  quickly  made.  From  5  to  20  c.c. 
are  injected,  according  to  the  size  of  the  lobe.  By  partially  withdrawing 
the  needle  and  reinserting  it,  contiguous  areas  may  be  injected  through 
one  puncture.  Dr.  Babcock  has  made  injections  in  his  office,  but  thinks, 
as  I  do,  that  this  is  not  to  be  commended.  I  prefer  to  have  the  patients 
remain  quiet  for  one-half  or  one  hour  after  the  injection  is  made.  The 
needle  punctures  are  covered  with  gauze  wrung  out  of  alcohol  for  a 
couple  of  hours.  Sloughing  has  never  occurred,  and  the  small  eschars 
on  the  skin  produced  by  the  needle  are  not  permanent.  The  needle 
should  penetrate  the  skin  as  nearly  as  possible  at  right  angles  in  order 
to  reduce  the  burning  to  a  minimum.  I  have  been  in  the  habit  of  hand- 
ling the  syringe  with  the  aid  of  forceps  and  gauze,  but  in  the  future  I 
shall  use  Babcock's  method  which  is  better.  He  wears  three  pairs  of 
gloves:  first,  a  pair  of  rubber  gloves  covered  with  thick  cotton  gloves, 
and  over  all  a  pair  of  rubber  gloves.  Most  patients  complain  immedi- 
ately after  the  injection  of  a  feeling  of  fulness  in  the  goiter  and  some  pain 
in  the  occiput,  but  the  discomfort  is  really  trifling.  The  injections  are 
to  be  repeated  until  the  desired  effect  is  attained.  If  one  is  using  the 
treatment  preparatory  to  thyroidectomy  then  it  is  well  to  repeat  the 
injections  every  two  or  three  days,  that  is,  if  more  than  one  is  neces- 
sary; but  if  one  has  decided  to  try  to  effect  a  cure  by  this  means,  it  will 
be  better  to  wait  a  week  to  ten  days  before  repeating  the  injections,  as 
indicated  above.  While  the  improvement  is  usually  marked  within  the 
first  forty-eight  hours,  it  does  not  reach  the  maximum  for  ten  days  to  two 
weeks.  It  is  better,  especially  in  the  large  goiters,  to  inject  two,  three 
or  more  areas  at  one  seance  than  to  make  the  injections  at  intervals. 
Indeed,  I  may  say  that  the  tendency  is,  as  experience  grows,  to  make 
large  and  multiple  injections  at  a  single  seance,  rather  than  to  make 
smaller  and  single  injections  and  to  repeat  the  seances.  In  some  cases 
with  small,  ill-defined  glands,  it  is  better  to  make  an  injection  through 
a  small  incision  in  the  midline,  done  under  local  anesthesia,  which  will 
enable  the  operator  to  do  the  work  under  the  guidance  of  the  eve." 


CHAPTER    XL VI. 

PREOPERATIVE  TREATMENT  OF   THE   PATIENT. 

When  the  patient  is  once  in  the  hospital  he  is  to  be  kept  in  bed  and 
given  rest.  Unless  there  should  be  vital  indication  to  do  otherwise,  not 
only  is  it  an  error,  but  it  is  criminal  to  operate  a  goiter  patient  without 
a  treatment  preparatory  to  operation.  This  preliminary  treatment  may 
last  only  a  few  days,  or  several  weeks,  just  as  the  case  mav  be. 

The  room  must  be  well  ventilated,  the  surroundings  must  be  quiet 
and  pleasant,  everything  must  be  done  to  gain  the  confidence  of  the 
patient  and  his  cooperation.  He  must  be  induced  to  "make  himself  at 
home."  Two  or  three  hours  a  day  he  will  be  allowed  to  sit  up  in  order 
to  break  the  monotony  of  the  rest  cure.  A  few  congenial  visitors  mav 
be  admitted. 

I  pon  entering  the  hospital,  if  the  bowels  have  not  been  regular,  a 
mild  laxative  can  be  given.  Subsequently  cathartics  must  be  given 
only  if  absolutely  necessary.  The  traditional  "cleaning  of  the  bowels" 
the  day  before  operation  must  be  discarded. 

Ten  to  fifteen  drops  of  Digalen  Cloetta  and  10  to  15  drops  of  tincture 
of  strophanthus  are  given  daily.  In  the  majority  of  cases  thev  have  a 
remarkable  toni-cardiac  effect.  If  not  well  tolerated  thev  should  be 
discarded.  If  bromides,  veronal,  tnonal,  baldrian  are  deemed  necessary, 
they  must  be  given. 

The  last  two  days  before  operation  the  patient,  especially  if  thvro- 
toxic,  is  given  150  grams  of  glucose  and  5  to  10  grams  of  bicarbonate 
of  soda  as  a  preventative  of  postoperative  acidosis.  (See  chapter  on 
Acidosis.) 

The  patient  must  be  kept  in  absolute  ignorance  of  the  day  and  time 
when  the  operation  is  to  take  place.  When  he  asks,  "Doctor,  when  am 
I  going  to  be  operated  upon":"  he  must  be  told  jokingly,  "That's  none 
of  your  business."     He  is  then  told  why. 

Menstruation  is  a  contra-indication  to  operation,  as  the  nervous  sys- 
tem of  these  patients,  especially  the  thyrotoxic  ones,  is  often  very  much 
disturbed  during  the  menstrual  cycle.  It  is  better  to  wait  until  that 
process  is  over. 

In  thyrotoxic  patients  no  surgical  preparation  ol  the  held  <>t  opera- 
twin  is  made  until  the  patient  is  on  tin-  operating  table.  In  simple,  non- 
complicated goiters,  three  or  tour  hours  prior  to  operation,  tin  field  of 
operation  may  In-  washed  with  soap  and  water,  cleansed  with  ether  and 


490  PREOPERATIVE  TREATMENT  OF  THE  PATIENT 

alcohol  and  then  protected  with  an  aseptic  dressing.  This,  however,  is  not 
necessary.  Of  late  I  do  not  resort  any  more  to  the  preliminary  surgical 
preparation.  I  found  that  simple  preparation  with  iodin  on  the  operat- 
ing table  is  just  as  satisfactory  as  when  combined  with  preliminary 
washing  with  soap,  water,  ether  and  alcohol  a  few  hours  previously. 
The  surplus  of  iodin  is  washed  off  with  alcohol.  When  using  iodin 
we  must  not  forget  that  its  disinfecting  and  penetrating  power  is  far 
greater  when  used  on  dry  skin  than  when  used  on  a  skin  which  has  just 
been  washed  and  cleansed.  Hence  the  necessity  of  performing  the 
preliminary  washing  with  soap,  water,  alcohol  and  ether  several  hours 
before  the  operation,  when  one  wants  to  resort  to  that  method  at  all. 
Forty-five  minutes  before  operation  the  patient  is  given  f  grain  of 
pantopon  and  ytw  grain  scopalamin.     (See  chapter  on  Pantopon.) 


CHAPTER    XL VI  I. 

OPERATING   ROOM  TECHNIC. 

On  the  table  the  patient  is  put  in  the  recumbent  position  with  a 
hard,  triangular  pillow  under  his  shoulders  so  as  to  overextend  the 
head.  The  purpose  of  this  is  to  make  the  neck  as  prominent  as  pos- 
sible and  to  put  the  thorax  in  a  dependent  position.  It  is  advisable,  if 
the  operating  table  permits,  to  elevate  the  upper  part  of  the  trunk 
slightly  and  to  lower  the  foot  so  as  to  obtain  an  oblique  elevated  posi- 
tion. This  lessens  the  venous  congestion  of  the  upper  part  of  the  body 
and  produces  a  certain  degree  of  cerebral  anemia,  thus  facilitating 
anesthesia  and  reducing  the  amount  of  anesthetic  used. 

The  field  of  operation  is  painted  with  iodin,  and  then  washed 
with  absolute  alcohol.  In  thyrotoxic  goiters,  where  one  wants  to  avoid 
iodin  intoxication,  McDonald's  solution  answers  the  purpose  very  well. 
I  have  used  it  with  entire  satisfaction.     Here  is  the  author's  formula: 

Acetone  (commercial) 40  parts 

Denatured  alcohol 60     " 

Pyxol 2     " 

The  operative  field  is  then  isolated  from  surrounding  parts  with 
sterilized  sheets.  The  Kocher  screen  for  protecting  the  field  of  opera- 
tion from  the  mouth  is  absolutely  necessary;  no  one  can  be  morally 
certain  of  his  asepsis  without  it.  The  hands  of  the  operator,  assistant  and 
nurses  are  washed  with  hot  water  and  soap  for  two  or  three  minutes, 
dried,  then  immersed  in  iodin  and  washed  with  alcohol.  There  should 
be  no  need  to  say  that  according  to  modern  views  on  asepsis,  no  surgeon 
who  is  really  anxious  to  be  thoroughly  aseptic  will  approach  the  oper- 
ating table  without  having  his  arms  protected  up  to  the  wrist  with 
sterilized  gowns,  his  hands  fitted  with  sterilized  gloves,  and  the  mouth 
and  head  covered  with  some  sterilized  device.  The  same  is  true  for  his 
assistants  and  nurses. 

Only  now  after  the  above  preparation  shall  the  anesthesia  be  started. 
Inasmuch  as  I  consider  the  anesthetic  one  of  the  greatest  dangers  in 
goiter  surgery,  I  aim  to  reduce  that  danger  to  a  minimum.  1  hat  is  the 
reason  why  I  give  the  anesthesia  at  the  last  moment  only,  and  cease  it 
before  the  operation  is  terminated.  In  the  greatest  number  of  cases  the 
element  of  excitement  and  fear  during  the  ten  to  fifteen  minutes  during 
which  the  surgical  preparation  is  being  made  prior  to  the  anesthetic  is 


492  OPERATING  ROOM  TECH  NIC 

negligible.  That  is,  at  least,  my  experience.  If  properly  explained  that 
it  is  done  for  his  own  benefit  and  safety,  the  patient  readily  consents  to 
being  anesthetized  in  the  operating  room.  Moreover,  the  presence  of 
the  surgeon  while  the  anesthetic  is  given  is  always  a  source  of  comfort 
to  the  patient,  as  usually  he  has  implicit  confidence  in  him,  while  he 
may  not  have  the  same  amount  in  the  anesthetist  whom  he  does  not 
know.  As  a  general  principle  general  anesthesia  must  be  always  light 
in  goiter  surgery.  Since  I  adopted  that  mode  of  doing,  after  having 
tried  everything  else,  my  postoperative  complications  such  as  hyper- 
thyroidism, acidosis,  etc.,  and  my  death-rate  have  been  reduced  con- 
siderably. The  more  severe  the  thyrotoxic  case  is,  the  stronger,  in  my 
judgment,  is  the  indication  to  reduce  the  period  and  amount  of  anes- 
thesia to  a  minimum,  or  even  to  resort  to  local  anesthesia. 

Before  the  present  great  war  broke  out,  I  used  systematically,  as 
advocated  by  Crile,  the  subcutaneous  infiltration  with  novocain.  Since, 
however,  novocain  remained  for  a  long  time  unavailable,  I  have  been 
compelled  to  do  without  it.  To  my  great  satisfaction,  I  have  not  noticed 
any  effect  for  the  worse  in  the  postoperative  welfare  of  my  patients. 
In  fact,  I  do  not  see  any  difference.  Consequently  I  have  given  up  the 
use  of  novocain  infiltration  in  conjunction  with  general  anesthesia. 

The  suture  material  used  is  silk  for  ligation  of  the  upper  poles,  and 
inferior  thyroid  arteries,  and  iodin  catgut  for  ligatures  and  sutures. 
Silk  is  used  on  account  of  its  non-resorbability. 


CHAPTER    XLVIII. 

POSTOPERATIVE  TREATMENT. 

As  soon  as  the  patient  is  brought  back  from  the  operating  room  a 
proctoclysis,  20  to  2^  drops  a  minute,  is  started.  I  use  the  following 
formula : 

Sodium  chloride 6.0 

Calcium  chloride 1.0 

Potassium  chloride 0.3 

Bicarbonate  of  soda          100. o 

Glucose i5°o 

Alcohol 20.0 

Aq.  dest iooo.o 

This  proctoclysis  is  kept  up  for  one  or  two  hours  and  then  stopped. 
A  few  hours  after  it  may  be  repeated  again.  It  is  an  excellent  means 
to  combat  thirst,  and  furthermore  has  the  great  advantage  of  increasing 
the  blood-pressure. 

Vomiting  is  present  in  a  small  percentage  of  cases,  but  is  rarely  so 
persistent  as  to  require  washing  out  of  the  stomach.  Transient  vomit- 
ing is  rather  an  advantage  since  it  clears  not  only  the  stomach,  but  also 
the  tracheo-broncho-pulmonary  apparatus.  As  soon  as  the  patient 
wants  it  he  may  have  cracked  ice  and  water  and  just  as  often  as  he 
wants  it,  even  if  vomiting  persists,  since  it  will  act  as  a  stomach  lavage. 
If,  however,  vomiting  should  remain  too  persistent  fluids  may  then  be 
withheld  for  a  time. 

If  the  cardiac  action  is  very  rapid,  ice-bag  on  the  heart  may  be  very 
beneficial.  If  the  cardiac  action  becomes  weak,  if  the  blood-pressure 
falls,  strophanthus,  digalen,  adrenalin,  are  given  hypodermically.  If 
symptoms  of  shock  appear,  the  usual  treatment  for  such  a  condition 
is  instituted.     Blood  transfusion  may  even  become  necessary. 

If  the  patient  is  very  restless,  nervous,  and  suffers  pain,  then 
pantopon,  codein,  bromides,  are  used.  If  one  fears  hyperthyroidism 
or  acidosis,  then  bicarbonate  of  soda,  and  glucose  are  resorted  to,  and 
the  patient  must  be  fed  with  fluid  food  as  soon  as  possible  even  the 
same  day  of  the  operation. 

Twenty-four  hours  after,  the  drain,  if  any  has  been  used,  is  removed. 
If,  however,  the  blood  is  still  fluid,  it  is  better  to  leave  the  drain  twenty- 
four  hours  longer. 

Forty-eight  hours  after  the  operation  ;i  cathartic  is  used,  such  as 
castor  oil,  salts,  or  citrate  of  magnesia.  As  soon  as  the  bowels  are  well 
open,  the  patient  is  given  solid  food. 

The  thread  for  intradermic  suture  is  removed  eight  days  after. 


CHAPTER    XLIX 


ANESTHESIA. 


The  ideal  means  of  anesthesia  for  human  surgery  has  not  yet  been 
found.  In  canine  surgery,  however,  we  can  say  that  a  sufficient  amount 
of  morphin  injected  subcutaneously  is  the  ideal  means  to  put  the  dogs 
under  complete  anesthesia.  A  few  minutes  after  the  subcutaneous 
injection  has  been  made,  a  reflex  vomiting  usually  takes  place;  then 
the  dog  quietly  goes  to  sleep,  and  about  one-half  to  one  hour  after,  when 
the  dose  has  been  sufficient,  the  dog  is  so  completely  anesthetized  and 
insensibility  lasts  so  long,  that  any  major  operation  can  be  performed 
without  the  slightest  indication  of  pain  or  struggle.  Even  hours  after 
the  operation  has  been  terminated,  the  influence  of  the  narcotic  may 
still  be  active.  Then  gradually  and  slowly  the  dog  emerges  from  his 
artificial  sleep.  Only  exceptionally  we  shall  find  dogs  which  seem 
refractory  to  the  influence  of  morphin.  No  ill  effects  remain  afterward. 
The  dose  of  morphin  required,  varies  of  course  with  the  weight  of  the 
dog,  and  its  nervous  temperament,  but  with  a  little  experience,  one  can 
easily  tell  the  amount  of  morphin  which  should  be  used.  As  a  rule  one 
to  two  grains  is  all  that  is  necessary.  Even  very  much  larger  doses  of 
the  drug  are  not  fatal  to  dogs.  The  experience  of  Dr.  Bromley  of  the 
Veterinary  Department  of  the  Ohio  State  University  at  Columbus, 
Ohio,  proves  this.  Wishing  to  kill  a  dog,  he  administered  to  it  a  sub- 
cutaneous dose  of  several  grains  of  morphin.  When  he  left,  the  dog 
looked  as  if  dead.  Great  was  his  surprise  on  the  following  morning  when 
he  came  back,  to  find  the  dog  gay  and  brisk.  That  day  a  new  method 
for  anesthetizing  canines  was  discovered.  The  advantages  of  this 
method  are  too  obvious:  no  need  of  an  anesthetist,  no  fear  of  these 
alarming  and  spectacular  respiratory  or  cardiac  collapses  which  still  too 
often  occur  with  other  means  of  anesthesia.  During  the  entire  artificial 
sleep  the  animal  breathes  regularly,  and  superficially,  while  the  pulse 
remains  good  and  strong  all  the  way  through.  It  is  a  delight.  But 
unfortunately  this  method  so  well  suited  to  the  canine  species  cannot 
be  applied  to  human  beings.  To  be  sure,  once  in  a  while  I  have  met 
with  patients  so  sensitive  to  pantopon-scopolamin  anesthesia  that  a 
moderately  large  dose  was  absolutely  sufficient  to  put  them  under 
complete  and  perfect  general  anesthesia,  allowing  me,  for  instance,  to 
perform  from  start  to  finish  the  complete  removal  of  an  intrathoracic 
goiter  without  necessitating  the  help  of  any  other  drug.     All  that  I  can 


AXESTHESIA  495 

say  about  it  is  that  I  have  never  operated  under  better  conditions  than 
in  these  cases.  Unfortunately  in  the  great  majority  of  cases  this  method 
is  insufficient.  The  amount  of  narcotic  required  to  produce  insensi- 
bility is  so  near  the  borderline  of  the  fatal  dose  that  to  use  it  would 
jeopardize  the  life  of  the  patient.  Let  us  hope  in  the  meantime  that 
we  may  some  day  find  a  means  to  anesthetize  our  patients  in  a  similar 
way  with  a  drug  just  as  effective  as  morphin,  pantopon,  etc.,  but 
deprived  of  their  disadvantages  and  dangers.  The  ideal  would  be  to 
find  a  means  to  induce  general  anesthesia  with  a  safe,  harmless 
medicament  injected  hypodermically. 

For  the  time  being  the  two  choice  methods  of  anesthesia  which  we 
have  at  hand  are:  local  anesthesia  with  novocain,  and  general  anesthesia 
with  chloroform,  ether,  and  nitrous  oxide.  Which  one  of  these  methods 
should  be  given  the  preference  in  goiter  surgery  and  especially  in  Base- 
dow's disease  ?  Should  we  use  local  anesthesia  only  or  the  general  one  ? 
And  if  we  decide  to  use  general  anesthesia,  to  what  drug  should  we  give 
the  preference,  to  chloroform,  ether,  or  to  nitrous  oxide  ?  All  these 
questions  are  by  no  means  settled  since  the  most  prominent  surgeons 
in  this  field  are  divided  in  their  opinions. 

Kocher,  Riedel,  Mikulicz,  Berg,  Ackermann  and  others  are  of  the 
opinion  that  general  anesthesia  is  dangerous  on  account  of  its  liability 
to  cause  asphyxia,  bronchitis,  pneumonia,  cardiac  collapse,  etc.  Indeed, 
they  say  how  often  during  general  anesthesia  do  we  not  see  alarming 
states  closely  resembling  death:  suddenly  respiration  and  heart  action 
stop,  the  face  becomes  pale,  livid  or  cyanotic,  pupils  become  dilated, 
and  for  a  few  seconds,  sometimes  a  minute,  despite  artificial  respira- 
tion, traction  of  the  tongue,  rhythmic  pressure  over  the  thorax,  etc.,  the 
function  of  the  pulmonary  and  cardiac  mechanism  remains  suspended. 
To  be  sure,  life  comes  back  but  it  does  it  slowly,  and  the  patient's  con- 
dition remains  precarious  throughout  the  operation.  There  can  be  no 
doubt  that  postoperative  deaths  in  many  instances  would  have  been 
avoided  if  such  cardiopulmonary  accidents  had  not  occurred.  In 
Basedow's  disease  the  majority  of  postoperative  accidents  arc-  attrib- 
uted by  these  authors  to  general  anesthesia.  Riedel  does  not  hesitate 
to  charge  general  anesthesia  with  the  majority  of  sudden  deaths. 
Kocher  attributes  his  low  mortality  to  the  use  of  local  anesthesia.  For 
these  authors  the  superiority  of  local  over  general  anesthesia  is  out  of 
the  question,  not  only  so  far  as  the  mortality  is  concerned,  bur  also  so 
far  as  postoperative  complications  are  concerned. 

On  the  other  hand,  \Ia\o,  Ilalstead,  Curtis,  (laiir,  Ochsner,  Crile 
and  others  believe  that  a  well-conducted  and  well-handled  general 
anesthesia  is  less  apt  to  !><•  followed  In  severe  consequences  than  a  local 
anesthesia.      In   fact,   during   the   latter   form   of   anesthesia,   the   ps\  chic 


496  ANESTHESIA 

emotions  and  shock  may  be  just  as  marked  as  with  general  anesthesia 
and  their  consequences  just  as  disastrous.  Certainly,  real  harm  may 
be  done  to  a  patient  by  the  mental  strain  and  physical  suffering  while 
undergoing  an  operation  without  being  unconscious.  With  local  anes- 
thesia the  operation  must  be  done  very  slowly,  much  time  must  be  lost 
in  encouraging  the  patient,  hence  a  prolonged  operation  and  increased 
chances  for  surgical  shock;  in  addition  during  operation,  on  account 
of  the  movements  for  defense  made  by  the  patient  in  order  to  escape 
pain,  there  is  an  increased  venous  hemorrhage.  Furthermore,  the 
veils,  cries,  and  sometimes  the  insults  which  the  patient  pours  out 
on  the  surgeon  who  is  endeavoring  to  do  his  best,  are  very  trying 
to  the  nervous  system  of  the  operator.  For  these  reasons  it  will  be 
easily  understood  why  many  surgeons  prefer  the  use  of  general  anes- 
thesia. There  is  therefore  a  matter  of  personal  cohesion  and  there  is 
certainly  a  great  deal  of  truth  in  what  Ochsner  says,  "The  patient's  con- 
fidence must  be  gained  before  the  administration  of  local  anesthesia, 
otherwise  the  patient  will  imagine  he  is  suffering  and  this  will  be  almost 
as  much  harm  to  him  as  actual  pain.  This  is  very  largely  a  personal 
matter.  Many  surgeons  have  the  full  confidence  of  all  their  patients 
and  for  them  it  is  not  difficult  to  employ  this  method." 

Before  drawing  our  own  conclusions  let  us  studv  a  little  more  fully 
the  dangers  connected  with  general  anesthesia. 

When  the  fumes  of  ether  or  chloroform  are  impure,  or  when  they  are 
inhaled  too  abruptly,  especially  if  the  patient  is  a  very  nervous  subject, 
reflex  accidents  may  occur  which  may  prove  very  alarming,  sometimes 
fatal.  They  may  occur  even  with  the  first  inhalations  of  the  drug.  They 
are  due  to  an  abnormally  intense  reflex  starting  in  the  naso-pharyngo- 
laryngeal  mucous  membrane,  even  before  the  fumes  have  reached  the 
pulmonary  alveoli.  We  know  experimentally  that  irritation  of  the 
nasal  and  laryngeal  mucous  membrane  may  cause  a  more  or  less  marked 
diminution  of  the  number  of  respirations  and  cardiac  beats;  it  may 
even  produce  respiratory  or  cardiac  collapses.  The  centripetal  routes 
taken  by  these  reflexes  are  the  branches  of  the  trigeminus  and  vagus 
nerves.  The  cardiac  collapse  is  due  to  a  centripetal  reflex  from  the 
vagus  nerve  which,  we  know,  is  a  moderator  of  the  cardiac  apparatus. 
This  inhibition,  however,  would  be  only  a  temporal)'  one  if  the  bulbar 
moderator)'  centers  would  not  soon  come  into  play  and  render  the  col- 
lapse permanent.  The  respirator)'  collapse  is  due  to  a  centripetal  reflex 
from  the  trigeminus,  resulting  finally  in  an  inhibition  of  the  respiratory 
centers. 

When  inhalation  of  the  anesthetic  takes  place  too  rapidly  there  is 
at  first  an  increased  heart  action  which  may  reach  I  50  to  200  beats, 
then  the  heart  action  diminishes  and  finally  a  cardiac  collapse  of  bulbar 


AX  EST  H  ESI  A  497 

origin  may  take  place.  When  too  much  anesthetic  is  given  paralysis 
of  the  respiratory  centers  takes  place. 

Besides  these  alarming  symptoms  there  are  others  of  less  importance 
but  nevertheless  very  annoying  to  the  patient,  such  as  coughing,  increased 
amount  of  saliva  due  to  centrifugal  reflexes  through  the  chorda  tym- 
pani  and  the  lingual  nerves,  etc.  All  these  reflexes,  of  course,  take  place 
mostly  during  the  early  period  of  anesthesia,  because  at  that  time  the 
reflex  power  of  the  nervous  centers  is  increased;  at  a  later  period  they 
become  greatly  diminished  or  suppressed. 

General  anesthesia  with  ether,  chloroform,  or  nitrous  oxide  has  other 
disadvantages.  It  is  accompanied  by  a  period  of  excitation  which  is 
very  unpleasant  for  the  patient  and  for  the  surgeon.  Furthermore,  it  is 
followed  either  during  or  after  the  narcosis  by  vomiting. 

To  sum  up,  the  dangers  connected  with  general  anesthesia  are  more 
than  one;  to  a  great  extent  they  can  be  eliminated  if  certain  rules  are 
followed.  In  order  to  avoid  respiratory  and  cardiac  collapses,  the  anes- 
thethic  should  be  very  pure:  it  should  be  given  with  extreme  care,  slowly, 
allowing  plenty  of  air  to  be  inhaled  with  the  anesthetic  agent.  The  excita- 
bility of  the  patient  should  be  diminished  by  a  preliminary  dose  of 
morphin,  or  better,  pantopon,  and  scopolamin.  Theoretically,  a  sufficient 
dose  of  atropin  would  be  ideal,  as  this  drug  suppresses  the  physiological 
function  of  the  cardiac  moderator)'  apparatus,  and  consequently  sup- 
presses at  the  same  time  the  risks  of  cardiac  collapse.  Unfortunately, 
this  drug  is  too  toxic  and  in  order  to  be  effective,  the  doses  would  have 
to  be  too  large.  But  to  return,  a  respirator)'  collapse  can  be  avoided 
with  a  careful  watching  of  the  course  of  the  anesthesia  and  the  patient. 
If  it  does  happen,  artificial  respiration  made  in  time  will  remedy  the 
accident. 

The  great  advantage  of  general  anesthesia,  with  volatile  narcotics 
such  as  chloroform,  ether,  nitrous  oxide,  is  that  in  case  of  necessity  it 
can  be  stopped  at  will  at  any  time.  The  patient  himself  is  his  best 
protection  as  he  eliminates  the  poison  with  each  respiration,  whereas  if 
the  anesthetic  drug  is  used  hypodermically  the  drug  injected  cannot 
be  withdrawn,  the  detoxication  lasts  a  long  time,  and  takes  place  only 
through  the  kidneys,  intestines,  etc. 

From  all  that  has  been  said,  it  follows  that  it  is  impossible  to  sit 
down  hard-and-rigid  rules  as  to  just  what  should  be  done  m  regard  to 
anesthesia  in  goiter  surgery.  It  would  be  ridiculous  to  proclaim  ex 
cathedra  that  general  anesthesia  should  be  used,  that  local  anesthesia 
should  or  should  not  be  used,  and  vice  versa.  Here  as  well  as  in  ;m\  other 
medical  question  there  is  a  just  milieu,  a  happy  medium. 

On  the  other  hand,  there  is  no  question,  tor  instance,  that  in  patients 
with  goiters  of  long  standing  and  large  size,  with  tracheal  deformations, 

32 


498  ANESTHESIA 

spells  of  suffocation,  chronic  congestion  of  the  entire  respiratory  appa- 
ratus, myocarditis,  arrhythmia,  marked  dyspnea,  general  anesthesia  is 
contra-indicated,  as  it  would  mean  enormous  risks  for  the  patient.  Con- 
sequently the  surgeon  and  the  patient  should  get  together  and  consent, 
the  one  to  perform  the  operation  under  increased  difficulties,  and  the 
other  to  undergo  the  operation  with  a  little  more  discomfort  and  pain. 
But  fortunately  the  majority  of  patients  with  simple  goiter  are  in  good 
general  health,  their  hearts  are  strong,  their  resistance  as  yet  has  not 
been  impaired,  and  the  goiter  has  not  had  time  to  do  very  much  harm. 
Under  such  conditions  it  is  really  more  satisfactory  for  everybody  con- 
cerned to  use  general  anesthesia  rather  than  a  local  one. 

In  Basedow  patients  profoundly  thyrotoxic  with  a  functionally  insuf- 
ficient myocardium,  kidneys,  and  liver,  there  is  no  doubt,  too,  that 
general  anesthesia  must  be  regarded  as  a  great  danger.  Local  anesthesia  is 
the  method  of  choice.  It  must  be  remembered  that  in  such  cases  any 
surgical  intervention,  however  small  it  may  be,  and  no  matter  what 
form  and  nature  of  anesthesia,  is  dangerous;  consequently,  how  to  pro- 
ceed is  a  matter  of  surgical  tact,  experience,  sound  judgment,  and  per- 
haps to  a  certain  extent,  of  personal  preference.  I  firmly  believe,  how- 
ever, that  a  well-managed  local  anesthesia  is  better  suited  to  these 
patients.  In  the  other  class  of  Basedow  patients  which  are  still  safely 
surgical,  a  well-conducted  general  anesthesia  carefully  given  and  carefully 
watched,  is  the  method  to  be  chosen.  In  doubtful  cases  especially  when 
local  anesthesia  cannot  be  employed  on  account  of  the  extreme  nervous 
condition  of  the  patient,  a  mixed  anesthesia  can  be  used  to  great  advan- 
tage in  the  following  manner:  a  reasonable  dose  of  pantopon-scopolamin 
is  given  one  and  one-half  hours  and  repeated  again  one-half  hour  before 
operation;  then  the  patient  is  brought  into  the  operating  room  and 
prepared  for  operation.  Only  then  general  anesthesia  is  started,  just 
enough  to  "slumber  away"  the  patient.  In  the  meantime  the  field  is 
thoroughly  infiltrated  with  0.5  per  cent,  solution  of  novocain,  a  con- 
siderable quantity  being  used.  The  general  anesthesia  is  stopped  off 
and  on;  if  necessary  a  few  drops  of  ether  are  given.  The  patient  is  all 
the  time  half-awake  but  unconscious  of  pain.  I  think  it  is  the  safest 
way  of  handling  these  cases.  Here,  too,  the  great  secret  of  success  is 
to  know  how  to  proportion  the  surgical  act  to  the  condition  of  the 
patient.  Too  often,  indeed,  failures  and  misfortunes  are  charged  to  the 
anesthetic,  when  they  recognize  as  the  sole  cause  a  lack  of  judgment 
and  of  experience  on  the  part  of  the  surgeon  and  an  injudiciously  per- 
formed operation,  either  because  "the  right  thing  has  been  done  at  the 
wrong  time,  or  the  wrong  thing  at  the  right  time." 

Chloroform,  Ether,  or  Nitrous  Oxide? — If  we  resort  to  general  anes- 
thesia, what  drug  shall  we  use? 


CHLOROFORM,  ETHER,  OR  XITROUS  OXIDE 


499 


It  is  now  universally  conceded  that  chloroform  is  a  dangerous 
anesthetic  agent.  The  statistics  of  Prof.  C.  Andrew,  made  in  1880  and 
based  on  200,893  anesthesias,  gives  1  death  for  2723  anesthesias  with 
chloroform.  The  record  of  Roger  Williams,  of  Bartholomew's  Hos- 
pital, London,  gives  10  deaths  out  of  12,368  anesthesias  with  chloroform. 
Gurlt,  out  of  201,224  anesthesias  found  88  cases  of  death.  The  average 
of  these  figures  gives  the  round  proportion  of  1  death  per  2000  anes- 
thesias with  chloroform.  Very  likely  this  average  is  low,  as  probably  a 
great  many  accidents  were  never  reported.  Chloroform  is  toxic  for  the 
blood,  as  it  destroys  a  certain  number  of  red  cells  and  diminishes  the 
activity  of  the  white  cells.  It  is  very  toxic,  too,  for  the  kidneys  and 
liver:  a  temporary  nephritis  and  hepatitis  not  infrequently  are  the 
sequelae  of  chloroform  anesthesia;  even  a  fulminating  icterus  in  abso- 
lutely normal  patients  has  been  observed  after  chloroform  anesthesia. 
Furthermore,  it  is  profoundly  toxic  for  the  heart,  and  is  an  intense 
depressor  of  the  blood-pressure.  For  all  these  reasons  chloroform  must 
be  discarded  in  goiter  surgery. 

For  the  time  being  the  most  popular  drug,  not  only  for  thyroid 
surgery,  but  for  any  kind  of  surgery,  is  ether.  It  is  the  one  used  by  such 
prominent  surgeons  as  Mayo  and  Ochsner  in  America,  and  in  Europe  by 
Garre,  Berard,  and  by  Kocher  when  obliged  to,  in  fact,  by  the  great 
majority  of  American  and  European  surgeons.  It  is  the  one  to  which 
I  give  preference.  It  is  superior  to  all  others  in  safety  and  range  of 
application,  its  record  for  mortality  being  about  1  to  10,000. 

Nitrons  oxide  anesthesia  is  not  practical  enough  to  be  safe.  While 
in  the  hands  of  Crile  it  has  so  far  given  excellent  results,  its  pre- 
paration and  administration  are  so  delicate  that  it  has  not  entered 
into  every-day  use  in  surgery.  We  might  even  say,  and  I  know  that 
the  same  view  is  held  by  Crile,  that  unless  very  chemically  pure  and  care- 
fully administered  by  an  expert  anesthetist,  this  means  of  anesthesia  is 
a  dangerous  one.  ''Enthusiastic  writers,"  says  Freeman  Allen  (he. 
cit.)y  "cite  the  statistics  of  Teter,  of  Cleveland,  and  the  tabulations  of 
Crile"  (Surgery,  Gynecology  and  Obstetrics,  191 1,  xiii,  170):  17,714 
administrations  by  Teter  of  nitrous  oxide  without  death  show: 


12,886  administrations 

lasted  less 

than    . 

5  minutes 

3.36s 

It 

5  to  15        " 

865 

<< 

15  to  30       " 

346 

it 

30  to  60          " 

228 

it 

i  to    2  hours 

22 

«< 

2  to    3      " 

2 

<< 

3  to    4     " 

17.714 


500  ANESTHESIA 

It  is  therefore  evident  that  the  majority  of  these  administrations  were 
for  dentistry  or  other  minor  surgical  procedures  requiring  brief  inhala- 
tions, and  not  for  major  surgery.  According  to  Freeman  Allen,  Thomas 
L.  Bennet,  of  New  York,  is  still  of  the  opinion  that  (loc.  cit.)  "while 
he  had  no  deaths,  alarming  states  have  several  times  appeared  with  such 
rapidity  and  so  little  warning  that  it  seems  probable  that  the  general 
adoption  of  this  form  of  anesthesia  would  lead  to  a  mortality  more 
nearly  approximating  if  not  exceeding  that  of  chloroform  and  ether." 

Freeman  Allen  has,  too,  met  with  alarming  states  similar  to  those 
mentioned  by  Bennet  {loc.  cit.).  "They  occurred  suddenly  without 
any  warning.  The  patient  suddenly  becomes  livid,  respiration  fails,  the 
pupils  dilate,  corneal  reflexes  become  faint  or  absent."  In  the  light  of 
the  above,  Allen  concludes  "that  gas  and  oxygen  anesthesia  is  not  the 
safest  anesthetic  method  in  major  surgery  and  it  would  seem  desir- 
able that  exploiters  of  this  method  in  citing  statistics  designed  to  show 
its  safety  should  carefully  separate  the  brief  administrations  required 
for  dentistry  and  other  minor  surgery  from  the  prolonged  administra- 
tions for  major  surgery;  otherwise  no  correct  estimation  as  to  its 
safety  in  the  latter  can  be  obtained." 

Undoubtedly,  nitrous  oxide  has  given  entire  satisfaction  to  Cnle  so 
far.  Nevertheless,  so  far  the  number  of  anesthesias  for  major  surgery 
is  not  large  enough  to  warrant  definite  judgment  of  the  method.  "The 
shortcomings  of  nitrous  oxide  anesthesia,"  says  Crile  (loc.  cit.),  are: 
"It  is  the  most  difficult  anesthetic  to  administer;  its  effects  are  fleeting; 
there  is  an  imperfect  relaxation  of  the  abdominal  muscles;  it  is  more 
expensive  than  ether,  and  there  is  more  venous  congestion.  The  anes- 
thetist must  be  an  individual  of  the  keenest  perception  of  the  precise 
condition  of  the  patient  at  every  moment,  i.  e.,  the  anesthetist  must  be 
a  delicate  human  recording  apparatus." 

Charles  K.  Teter  (Jour.  Am.  Med.  Assn.,  Nov.  23,  1912,  lix)  says: 
"That  nitrous  oxide  is  contra-indicated  in  children  under  five  years  of 
age,  in  old  people  in  whom  arteriosclerosis  is  present.  Nitrous  oxide  as 
an  anesthetic  is  not  ideal  for  major  surgery  in  patients  possessing  a 
strong,  vigorous  constitution,  or  extremely  nervous  temperaments,  or 
in  those  addicted  to  drug  habits  or  the  excessive  use  of  tobacco.  In 
other  words,  any  patient  who  requires  a  large  amount  of  general  anes- 
thesia is  not  a  good  gas-oxygen  subject  for  control,  owing  to  the  lighter 
form  of  anesthesia  induced  by  nitrous  oxide.  The  ideal  patients  for 
nitrous  oxide  and  oxygen  anesthesia  are  the  very  ill,  the  anemic,  the 
debilitated,  those  possessing  a  low  vitality  from  any  cause,  in  short,  all 
cases  except  those  requiring  a  powerful  anesthetic  agent." 

In  the  light  of  the  above  we  can  conclude  that  nitrous  oxide  anes- 
thesia is  not  yet  a  practical  method.     We  can  even  say  that  except  in 


LOCAL  ANESTHESIA  501 

the  hands  of  a  very  few  as  Cnle,  Bloodgood,  for  instance,  the  method  is 
dangerous.  It  is  impossible  for  me  to  overlook  the  fact  that  in  the 
practice  of  one  of  my  colleagues,  3  cases  of  sudden  death  occurred  under 
nitrous  oxide  anesthesia;  yet  the  anesthetic  was  given  by  an  expert 
anesthetist  and  for  simple  operations  as  appendicitis,  hernia,  etc.  If  we 
stop  to  think  that  these  deaths  occurred  in  a  series  of  about  150  anes- 
thesias with  nitrous  oxide,  we  find  the  percentage  of  death  to  be  about 
2  per  cent.  Of  course  I  am  ready  to  admit  that  this  might  be  only  a 
coincidence.  I  am  not  trying  in  any  way  to  discredit  the  method,  but 
I  am  trying  to  remain  objective. 

LOCAL    ANESTHESIA. 

Cocain  is  still  the  most  powerful  among  the  local  anesthetics,  but  its 
toxicity  forbids  its  being  used  too  freely.  The  drug  of  choice  for  local 
anesthesia  for  the  time  being  is  novocain.  It  possesses  a  far  more  superior 
anesthetizing  power  than  stovain,  tropocain,  and  about  an  equal  power 
with  cocain.  On  the  other  hand,  novocain  is  twice  less  toxic  than  cocain. 
The  injection  of  0.5  per  cent,  solution  hypodermicallv  is  slightly  pain- 
ful if  novocain  is  dissolved  in  simple  water,  but  becomes  absolutely 
painless  if  dissolved  in  normal  salt  solution.  Anesthesia  with  novocain 
is  complete  eight  to  ten  minutes  after  the  injection  has  been  made  and 
is  nearly  always  perfect  in  the  injected  area.  It  lasts  about  half  an 
hour.  The  period  of  anesthesia  may  be  prolonged  by  adding  adrenalin 
to  the  novocain  solution.  The  following  formula  is  the  one  which  gives 
the  best  results: 

Salt  solution ...      100. o  gms. 

Novocain ....         0.5       " 

Adrenalin  1:1000  25       drops. 

It  a  2-c.c.  syringe  is  used  for  injection,  each  syringe  contains  0.01 
gm.  of  novocain  and  one-half  drop  of  solution  of  adrenalin  1  :  1000. 
This  mixture  of  novocain-adrenalm  possesses  a  powerful  anesthetizing 
capacity  which  is  about  equal  to  that  of  cocain;  its  effects  last  about  an 
hour.  It  is  absolutely  painless  and  while  novocain  alone  has  no  effect 
upon  the  bloodvessels,  the  mixture,  novocain-adrenalm,  causes  a  pro- 
nounced vasoconstriction  lasting  several  hours.  The  adjunction  of  adre- 
nalin does  not  increase  the  toxicity  of  the  drug,  consequently  large  doses 
of  the  solution  can  be  used  in  the  same  patient.  Chaput,  using  it  for 
the  removal  of  a  cancer  of  the  breast,  went  so  far  as  to  use  140  c.c.  of 
0.5  per  cent,  solution.     No  ill  effects  wen-  observed. 

It  must  be  always  remembered  that  the  mixture  novocain-adrenalin, 
does  not  keep  very  long.  //  must  he  freshly  prepared  each  time  before 
using  it.     Inasmuch  as  a  solution  of  novocain,  just  as  that  of  adrenalin. 


502  ANESTHESIA 

kept  separately  keeps  perfectly  for  a  long  time,  it  is  better  to  have  both 
at  hand  always  separately  prepared  and  to  mix  them  only  just  before 
the  operation.  The  novocain  solution  can  be  sterilized  at  the  autoclave 
without  injuring  its  anesthetizing  properties.  So  far  as  adrenalin  is 
concerned,  we  have  the  choice  between  the  adrenalin  itself,  which  is 
extracted  from  the  suprarenal  bodies,  and  the  one  synthetically  obtained 
and  called  suprarenin.  Theoretically,  supraremn  offers  greater  advan- 
tages than  adrenalin.  Being  synthetically  prepared,  it  is  always  iden- 
tical with  itself,  consequently  its  properties  are  constant.  Furthermore, 
it  can  be  sterilized  with  impunity  at  the  autoclave,  whereas  adrenalin 
is  readily  oxidized  and  when  sterilized  loses  a  great  part  of  its  proper- 
ties. The  oxidation  and  consequently  the  deterioration  of  the  solution 
are  recognized  by  the  fact  that  the  solution  becomes  pink,  then  red  and 
finally  brown  in  color.  Adrenalin  chloride,  however,  which  is  an  addi- 
tional product  formed  by  the  action  of  dilute  hydrochloric  acid  upon 
adrenalin  seems  to  be  a  quite  stable  product.  When  in  ampoules, 
according  to  Rowe,  it  may  be  heated  to  the  temperature  of  boiling  water, 
and  can  be  sterilized  several  times  in  succession  without  loss  of  activity. 
When  exposed  to  the  air,  it  may  be  sterilized  twice  without  loss  of 
activity. 

There  are  on  the  market  small  tablets  of  novocain  and  adrenalin 
already  mixed  in  the  desired  proportions.  These  tablets,  of  course,  are 
of  the  greatest  convenience,  but  according  to  Piquand,  they  are  far  from- 
having  the  same  anesthetizing  power  that  is  possessed  by  a  mixture 
prepared  on  the  spot  just  before  the  operation. 

Local  anesthesia  should  never  be  employed  unless  the  patient  is 
lying  down.  If  the  injection  is  made  in  the  sitting  posture,  collapse  is 
liable  to  take  place.  This  is  not  at  all  to  be  wondered  at  when  we  know 
that  the  injected  solution  of  novocain-adrenahn  does  not  exert  its  action 
locally  only,  but  that  to  a  certain  extent,  its  influence  extends  to  the 
entire  organism.  As  adrenalin  is  one  of  the  most  powerful  vasocon- 
strictive drugs,  vasoconstriction  takes  place  in  the  brain,  producing  cere- 
bral anemia,  and  hence  collapse.  If  the  patient  is  in  the  dorsal  decubi- 
tus, the  chances  for  collapse  are  less  marked  since  the  lying  posture 
favors  congestion  of  the  brain.  Before  using  local  anesthesia  it  is  pru- 
dent whenever  it  is  possible  to  give  a  dose  of  pantopon  and  scopolamin 
half  an  hour  before.  Scopolamin,  being  a  vasodilatator,  is  especially 
indicated  in  local  anesthesia,  as  it  more  or  less  counter-balances  the 
general  effects  of  adrenalin. 

Technic  of  Local  Anesthesia. — Although  apparently  simple,  this  technic 
requires  skill  and  experience.  When  once  the  course  of  the  future 
incision  is  decided  upon,  one  of  its  ends,  the  nearest  to  the  surgeon, 
is   seized   between   the  thumb  and  index  finger  of  the   left   hand   so   as 


LOCAL  ANESTHESIA 


503 


to  form  a  thin,  cutaneous  fold  which  is  then  lifted.  The  fine  needle 
of  a  syringe  loaded  with  0.5  per  cent,  solution  of  novocain-adrenalin  is 
inserted  into  the  derm  of  the  skin  and  not  in  the  subcutaneous  tissue. 
A  small  quantity  of  the  anesthetic  is  then  forced  into  it.  At  once  it 
forms  a  white  bleb  1  cm.  in  diameter,  which  is  the  best  proof  that  the 
injection  is  really  intradermic.  The  needle  is  then  pushed  forward  and 
while  pushing,  a  continuous  pressure  upon  the  piston  of  the  syringe 
forces  continuously  some  of  the  anesthetic  solution  into  the  tissues,  thus 
rendering  the  injection  painless. 


Fig.  84. — Local  anesthesia.  I  he  picture  shows  a  row  of  intradermic  blehs  along  the 
line  of  future  low-collar  incision.  The  picture  shows,  furthermore,  where  the  injection 
will  have  to  be  made  in  the  prethyroid  muscles  after  the  two  skin  flaps  have  been  retracted 
before  undertaking  their  division. 


A  well-managed  local  anesthesia  should  cause  only  at  one  time  a 
little  pain,  and  that  is  when  the  needle  goes  through  the  skin  for  the 
first  time.    Then  the  patient  should  be  warned  that  he  is  going  to  teel  a 


504 


ANESTHESIA 


pricking  pain.     In  the  subsequent  injections,  as  the  needle  goes  through 
the  anesthetized  area,  no  pain  should  be  felt.     These  intradermic  injec- 


Fig.  85. — Local  anesthesia.     Local  anesthetic  is  injected  into  the  whole  field  of  operation 
in  order  to  render  anesthesia  as  perfect  as  possible. 


w/ 


Fig.  86. — 3  and  5  are  made  not  only  subcutaneously  but  also  deeply  behind  the  sterno- 
cleidomastoid muscle  so  as  to  reach  the  bulk  of  the  superficial  cervical  plexus. 

tions  are  repeated  until  the  entire  line  of  the  future  incision  forms  a 
continuous  row  of  blebs  from  one  to  two  centimeters  in  width  (Fig.  84). 


LOCAL  AXESTHESIA 


505 


When  once  the  site  of  the  future  incision  has  been  thoroughly  anes- 
thetized, subcutaneous  injections  of  novocain-adrenalin  are  made  along 
the  same  course.  Then  the  anesthetizing  solution  is  forced  into  the 
entire  subcutaneous  region  above  and  below  the  incision,  not  only  where 
the  upper  and  lower  flap  will  be  dissected  but  also  in  the  entire  region 
neighboring  on  the  field  of  operation  (Figs.  85  and  86),  as  the  sterno- 
cleidomastoid region,  the  thyroid  cartilage  region,  etc.  The  more  per- 
fect the  infiltration  of  the  cervical  region  with  the  anesthetizing  solution, 
the  less  will  be  felt  the  pain  during  operative  manipulations. 


FlG.  87. — Local    anesthesia.     Showing    how  and  where    to  inject  the  local    anesthetic   in 
order  to  fully  anesthetize  the  deep  tissues. 


Eight  or  ten  minutes  should  elapse  before  cutting  is  done.  Only 
then  the  incision  and  the  preparation  of  the  upper  and  lower  flaps  can 
be  made  without  pain. 

The  Upper  and  lower  Maps  being  retracted,  the  cervical  fascia  and 
its  underlying  muscles  are  then  infiltrated  with  novocain-adrenalin 
solution,  especially  at  the  point  where  the  incision  will  take  place 
(Fig.  S4).  As  the  thyroid  is  not  sensitive  it  will  not  be  necessary  to 
inject  any  anesthetic  into  it.  The  two  regions  where  some  pain  is  felt 
are  the  upper  and  lower  poles.  They  are  consequently  thoroughly  anes- 
thetized with  the  mixture.      Before  luxating  the  goiter,  as  this  part  of 


506  AN  EST  H  EI  I A 

the  operation  is  very  painful,  it  is  well  to  inject  some  novocain-adrenalin 
solution  into  the  surgical  capsule.  The  same  must  be  done,  too,  around 
the  trachea  and  esophagus,  and  on  the  posterior  surface  of  the  thyroid 
(Fig.  87),  bearing,  however,  in  mind  the  danger  zone.  When  dealing 
with  the  isthmus,  novocain-adrenalin  solution  must  be  injected  above 
and  below  the  isthmus  and  between  the  latter  organ  and  the  trachea 
(Fig  87). 

If  one  follows  carefully  the  three  following  rules,  local  anesthesia 
will  give  in  a  great  many  instances  very  satisfactory  results. 

1.  One  should  wait  eight  to  ten  minutes  after  infiltration  is  com- 
pleted before  beginning  the  operation. 

2.  The  surgeon  should  always  keep  within  the  limits  traced  by  the 
injection.  As  soon  as  he  steps  outside  of  these  limits  pain  is  sure  to 
follow. 

3.  Operation  should  be  done  carefully,  methodically,  with  gentle- 
ness. Roughness  does  not  agree  with  local  anesthesia.  In  this  respect 
the  assistants  with  their  retractors,  if  not  intelligently  controlled,  can 
do  a  great  deal  of  harm. 

Intratracheal  Insufflation  Anesthesia  in  Thyroid  Surgery  seemed  at 
first  to  be  full  of  promise.  I  have,  however,  found  it  disappointing.  Just 
in  the  cases  where  it  was  expected  to  be  the  most  useful,  namely,  in 
goiters  with  pressure  symptoms  it  failed  to  fulfil  its  expectations. 

1.  As  is  known,  before  the  intratracheal  insufflation  can  be  used  the 
patient  must  be  put  to  sleep  in  the  usual  way.  It  is  only  when  the  patient 
is  anesthetized  that  the  catheter  is  passed  into  the  trachea.  Now  then, 
in  goiter  causing  pressure  symptoms,  suffocation,  as  a  rule,  occurs  with 
the  first  inhalations  of  ether,  so  that  one  has  no  time  to  resort  to  the 
intratracheal  insufflation  method;  the  operation  must  be  very  quickly 
done  in  order  to  relieve  pressure  upon  the  trachea,  or  tracheotomy  must 
be  performed  a  tout  prix — at  all  costs — otherwise  the  patient  will  be 
dead;  consequently  the  object  of  intratracheal  insufflation  is  defeated. 

2.  Since  in  order  to  pass  the  catheter  into  the  trachea  the  head 
must  be  excessively  extended,  if  the  pressure  symptoms  are  already 
marked,  suffocation  is  bound  to  be  made  much  worse  by  the 
hyperextension  of  the  head,  hence  the  necessity  to  pass  quickly  the 
catheter  into  the  larynx.  This  is  not  always  easy.  I  confess  that  in 
some  of  these  distressing  moments  I  have  failed.  Mucus  is  so  abundant 
and  congestion  is  so  marked  that  the  process  is  not  an  easy  matter 
by  any  means.  Add  to  it  all  that  the  time  you  have  at  your  disposal 
is  so  short  that  you  are  confronted  with  the  dilemma:  either  to  pass 
the  tube  or  to  let  the  patient  die.  Each  second  lost  in  the  attempt 
means  that  much  less  time  left  to  reach  the  windpipe  by  the  cervical 
route  through  an  incision,  if  the  catheter  cannot  be  passed  into  the 
trachea.     Knowing  that  after  thyroidectomy  a  thymic  dyspnea  is  liable 


LOCAL  AXESTHESIA  507 

to  occur  most  unexpectedly,  I  always  have  the  intratracheal  insufflation 
apparatus  in  the  room  of  the  patient  read)'  for  an  emergency.  In  3 
cases  where  I  had  such  accidents  I  failed  to  pass  the  tube  into  the 
trachea. 

3.  If  the  trachea  is  displaced  and  compressed,  the  catheter  often 
cannot  be  made  to  pass  the  point  of  compression. 

4.  Robinson  collected  1400  cases  of  intratracheal  anesthesias  with 
7  deaths,  1  from  lung  rupture  and  1  from  emphysema. 

Pantopon-scopolamin. — Nowadays  anesthesia,  be  it  general  or  local, 
is  obtained  through  a  mixed  narcosis:  a  preliminary  dose  of  an  hypnotic 
of  some  sort  is  given  hvpodermicallv  before;  and  the  effect  of  this  adds 
to  that  of  the  subsequent  drug  used  for  general  anesthesia.  Up  to  now 
morphin  has  had  the  priority;  lately,  however,  pantopon  seems  to  take 
its  place  very  advantageously. 

Pantopon  is  superior  to  morphin  for  manv  reasons.  It  contains  the 
totality  of  the  useful  alkaloids  of  opium  soluble  in  water,  and  it  can  be 
injected  hvpodermicallv  just  as  well  as  morphin.  No  doubt  morphin 
possesses  the  analgesic  and  hypnotic  properties  of  opium;  but  opium 
owing  to  the  presence  of  its  various  alkaloids  possesses  other  secondary 
actions  which  morphin  has  not.  For  instance,  it  has  a  sedative  action 
over  the  nervous  system,  a  tonic  influence  over  the  cardiac  system,  and 
an  antinauseous  effect  which  morphin  certainly  has  not.  Pantopon 
may  be  regarded  as  a  purified  opium.  All  the  harmful  alkaloids  have 
been  eliminated,  and  the  useful  retained.  Roughly  speaking,  pantopon 
contains  50  per  cent,  of  morphin,  20  per  cent,  of  narcotin,  2  per  cent,  of 
codein  and  papaverin,  and  1  per  cent,  of  thebain  and  narcein.  This  drug 
has  been  advocated  by  Sahli,  of  Berne,  in  collaboration  with  Scharges. 

In  equivalent  doses,  morphin  may  be  slightly-  more  analgesic  and 
probably  has  a  more  rapid  action,  but  the  digestive  tolerance  of  panto- 
pon is  far  superior.  Vomiting  after  the  use  of  pantopon  is  less  frequent 
than  after  the  use  of  morphin.  The  tonic  influence  over  the  cardiac 
system  is  manifest  with  pantopon.  The  paralytic  influence  of  morphin  is 
well-known;  according  to  Wertheimer,  Lowy,  and  Bergien,  the  paralytic 
influence  of  pantopon  on  the  respiratory  centers  is  far  less  accentuated. 

After  pantopon  has  been  given  hvpodermicallv,  in  association  with 
scopolamin,  the  patient  falls  into  a  dozing  sleep — the  " Dammerschlaf" 
of  the  Germans.  The  active  movements  cease;  the  sensation  of  pain  is 
diminished  to  a  great  extent;  consciousness  although  still  present  is  con- 
siderably reduced;  the  patient  sleeps,  but  may  be  awakened  by  call, 
light,  or  sound.  In  some  instances  the  patient  is  so  thoroughly  anes- 
thetized that  a  complete  operation  may  be  performed  without  his  knowl- 
edge. Naturally,  such  results  vary  with  the  doses  employed  and  the 
individual's  sensibility.  I  have  seen,  although  not  frequentlj  ,  patients 
who  did  not  respond   to  the  action  of   pantopon  and   to  whom  morphin 


508  ANESTHESIA 

had  to  be  given  instead.  They  were  nervous,  mostly  thyrotoxic  patients, 
in  whom  the  cerebrospinal  system  was  greatly  excited.  However,  this 
lack  of  response  happens  with  morphin,  too.  As  a  rule  women  react 
more  readily  than  men,  consequently  smaller  doses  of  pantopon  may  be 
given  to  them.  Pantopon  may  be  given  to  children  as  well,  without 
any  danger. 

To  sum  up,  pantopon-scopolamin  in  surgical  work  seems  to  have 
great  superiority  over  the  morphin-scopolamin  combination.  It  dimin- 
ishes the  vomiting  to  a  great  extent  during  and  after  the  operation.  It 
reduces  materially  the  quantity  of  the  drug  used  to  induce  general 
anesthesia  and  diminishes  the  preanesthetic  excitation  period.  It  has 
not  the  same  constipating  effect  on  the  intestines  as  morphin.  The 
average  dose  is  from  2  to  4  cgms.  of  pantopon  and  from  0.0003  to  0.0005 
cgm.  of  scopolamin.  As  a  general  rule  we  can  say  that  the  dose  of 
pantopon  which  must  be  employed  is  about  double  the  one  of  morphin; 
consequently  in  cases  where  1  cgm.  of  morphin  would  be  given,  2  cgms. 
of  pantopon  will  be  necessary  to  obtain  the  corresponding  effect. 

One  must  be  careful  in  the  handling  of  scopolamin.  It  is  best  to 
have  the  solution  freshly  prepared  each  time  before  using.  Pantopon 
and  scopolamin  may  be  given  simultaneously  or  separately.  However, 
the  majority  of  authors  claim  that  it  is  better  to  give  them  separately 
and  at  intervals  of  one-half  hour. 

In  goiter  surgery  pantopon-scopolamin  is  used  to  the  best  advan- 
tage in  the  following  manner:  1  grain  of  pantopon  and  j^  grain  of 
scopolamin  are  given  one-half  hour  before  operation.  If  a  patient 
shows  an  idiosyncrasy  to  the  drug,  the  operation  must  be  postponed 
a  day  or  two  in  order  to  permit  elimination.  I  have  been  using 
pantopon-scopolamin  for  five  years  now  and  have  not  met  with  such  a 
necessity. 

No  medicament  is  ideal  and  the  pantopon-scopolamin  combination 
has  its  weak  points,  too.  As  said  before,  in  alcoholic  and  Basedow 
patients,  instead  of  producing  a  sedative  effect  on  the  nervous  system 
it  may,  on  the  contrary,  cause  an  excitement  of  it;  this  is  rare,  however, 
and  also  happens  with  morphin.  After  the  use  of  pantopon-scopolamin 
the  patient  often  complains  of  dry  mouth  and  thirst.  This  sensation  is 
not  due  to  pantopon  but  to  the  scopolamin,  since  we  know  that  the  latter 
drug  influences  the  terminal  ends  of  the  secretory  nerves.  This  action 
is  purposely  counted  upon  in  giving  ether  anesthetic,  as  it  prevents  the 
troublesome  formation  of  mucus  in  the  bronchotracheal  tract.  The 
really  greatest  danger  of  pantopon-scopolamin  is  its  liability  of  causing 
a  paralysis  of  the  respiratory  centers.  As  said  before,  this  liability  is 
less  marked  for  pantopon  than  for  morphin.  Large  doses  should  not 
be  used  in  weak  people,  in  old  patients,  and  in  those  with  disturbances 
of  the  respiratory  apparatus. 


CHAPTER    L. 

POSTOPERATIVE   COMPLICATIONS. 

Shock. — The  phenomenon  known  as  shock  was  a  condition  recog- 
nized as  early  as  1568  by  Clowes,  and  by  Weismann  in  1719,  who  spoke 
of  it  as  a  condition  probably  caused  by  the  presence  of  a  foreign  bodk- 
in the  wound  or  blood.  The  word  "shock"  was  first  used  clinically  in 
the  eighteenth  century  and  was  meant  to  express  the  notion  of  grave 
organic  disturbances  unaccompanied  by  demonstrable  organic  changes. 
It  is  difficult,  not  to  say  impossible,  to  give  a  clear,  concise  and  correct 
definition  of  shock.  The  word  does  not  represent  a  definite  symptom, 
but  a  symptom-complex  dependent  upon  more  than  one  causative  fac- 
tor. The  best  definition  of  shock  which  I  know  of  is  the  one  given  by 
the  elder  Gross  when  he  said,  "Shock  is  the  rude  unhinging  of  the  entire 
machinery  of  life."  Clinically,  we  call  shock  a  condition  characterized 
by  a  low  blood-pressure,  a  soft,  rapid,  and  thready  pulse,  a  marked 
pallor  oi  the  mucous  membrane  and  integuments,  a  rapid  and  superficial, 
and  often  irregular  respiration,  air  hunger,  subnormal  temperature,  cold 
and  moist  extremities  and  finally  a  more  or  less  marked  degree  of  stupor, 
with  diminished  or  suppressed  sensibility  to  painful  stimuli;  sometimes 
there  is  mental  anxiety  without  outcry.  It  is  an  error  to  make  a  differ- 
ence between  shock  and  collapse:  they  are  the  same  thing. 

In  the  last  few  decades  explanations  and  theories  have  succeeded 
one  after  the  other,  each  one  trying  to  locate  the  "unhinging"  at  the 
door  of  some  organ  or  function,  but  everyone  of  these  theories  has  failed 
to  solve  the  problem.    The  most  important  theories  regarding  shock  are: 

1.  \  asomotor  exhaustion  and  paralysis. 

2.  Cardiac  spasm  and  eventual  failure. 

3.  Inhibition  of  the  function  of  all  the  organs. 

4.  Deficiency  of  carbon  dioxide  in  the  blood  01  acapnia. 

5.  Morphological  changes  in  the  ganglion  cells. 

6.  Loss  of  vasomotor  control  due  to  inhibition  from  afferent  sensory 
influences. 

7.  Primary  suprarenal  exhaustion. 

1.  Vasomotor  Exhaustion  and  Paralysis.  Nearly  half  a  century  ago 
Keen,  Mitchell,  Moorehouse  and  Fischer  advanced  the  theory  of  vaso- 
motor exhaustion  with  flooding  of  the  splanchnic  veins  and  contraction 
of  the  peripheral  vascular  system.  This  theory  was.  for  a  time,  rejuve- 
nated by  (Vile.     lie  argued,  "that  the  essential  phenomenon  of  shock 


510  POSTOPERATIVE  COMPLICATIONS 

was  low  blood-pressure,  that  since  there  was  no  demonstrable  lesion  in 
fatal  cases  and  no  later  effects  in  those  who  recover,  we  must  assume 
exhaustion  rather  than  structural  lesions  to  be  the  cause  of  this  fall." 
This  exhaustion  is  not  located  in  the  heart.  The  accelerated  heart 
action  must  be  taken  as  evidence  of  the  effort  of  the  regulating  centers 
to  recover  the  lost  blood-pressure.  The  splendid  action  of  the  heart 
under  these  conditions  after  infusion  of  the  salt  solution  proves  it  to  be 
well  capable  of  further  action.  This  exhaustion  is  located  neither  in 
the  cardio-inhibitory  nor  in  the  cardio-acceleratory  centers,  as  shock 
may  occur  even  when  the  cardiac  nerve  supply,  namely,  the  vagi  and 
sympathetic  branches  have  been  severed.  The  peripheral  nerve  vascu- 
lar mechanism  cannot  be  incriminated,  as  it  responds  to  stimulants 
always.  Finally,  the  vasomotor  centers  are  not  exhausted  either  because 
these  centers  respond  to  electric  stimulation  even  when  the  organism  is 
in  a  state  of  profound  shock.  Porter  and  Quimby  showed  that  the 
central  end  of  the  sciatic  nerve  can  be  stimulated  for  hours  without 
causing  any  fall  of  pressure.  On  purely  empirical  grounds  Malcolm,  of 
England,  claimed  that  the  vasomotor  centers  not  only  were  not  exhausted, 
but  were  overactive  throughout  shock,  and  that  the  peripheral  vascular 
system  instead  of  being  relaxed  was  contracted.  He  based  his  conclu- 
sions on  the  fact  that  in  shock  the  surface  of  the  body  is  cold,  the  skin 
pale,  the  pulse  small,  the  mucous  membrane  blanched,  and  the  bleeding 
from  the  wound  surface  scant.  Sheen  very  judicously  remarked  that  in 
shock  an  unduly  large  proportion  of  blood  was  in  the  abdomen.  Accord- 
ing to  Janeway  and  Ewing,  it  is  "as  though  the  branches  of  the  mesen- 
teric arteries  emptied  into  a  large  reservoir  with  perfectly  flaccid  walls, 
into  which  they  bled  to  death.  The  aptness  of  the  comparison  of  the 
splanchnic  area  to  a  flaccid  rubber  bag  is  made  more  apparent  by 
pressure  on  the  abdomen:  the  blood-pressure  can  be  raised  "at  will  by 
this  procedure."  This  will  explain  why  the  peripheral  vessels  are  small. 
Henderson  claimed  that  "in  shock  the  vasomotor  center  does  its  full 
duty  almost  to  the  last;  the  fall  in  blood-pressure  is  due  to  the  diminu- 
tion of  the  volume  by  transudation  of  its  fluid  constituents  out  of  the 
vessels  into  the  tissues.  In  his  experiments  on  dogs,  he  noticed  that 
they  died  of  "respiratory  failure  long  before  pressure  had  become  very 
low."  This,  I  have  experienced  clinically,  too,  in  one  of  my  patients 
who  died  in  a  state  of  profound  shock  after  thyroidectomy  performed 
under  local  anesthesia.  In  that  case  respiration  had  stopped  a  long 
time  before  cardiac  action  had  ceased.  Seelig  and  Lyon  very  elegantly 
demonstrated  that  in  normal  animals  stimulation  of  the  central  end  of 
the  vagus  nerve  when  divided  causes  a  rise  in  blood-pressure  and  that 
this  rise  occurs  even  when  the  animals  are  in  the  most  profound  degree 
of  shock,  thus  showing  that  the  vasomotor  centers  are  still  capable  of 


MORPHOLOGICAL  CHAXGES  IX   THE  GAXGLIOX  CELLS        511 

activity.  We  must  consequently  admit  that  low  blood-pressure  is  an 
important  accompanying  symptom  of  shock,  but  that  it  is  not  the 
primary  cause  of  it. 

2.  Cardiac  Spasm  and  Eventual  Failure. — Boise  attempted  to  prove  that, 
on  account  of  peripheral  trauma,  the  heart  is  overstimulated  and  thrown 
into  spasm,  hence  an  increased  systole,  and  decreased  diastole,  a  lessened 
output  of  blood  from  the  heart,  and  consequently  a  lowered  pressure.  As 
Seelig  says,  Boise  fails  to  explain  why  the  work  of  numerous  investi- 
gators who  have  thoroughly  isolated  the  heart  from  its  afferent  paths 
have  still  been  able  to  produce  shock. 

3.  Inhibition  of  the  Function  of  all  Organs. — Meltzer,  reviewing  all  the 
more  recent  theories  of  the  nature  of  shock,  ventures  the  assumption 
"that  various  injuries  which  are  capable  of  bringing  on  shock  do  so  by 
the  inhibition  of  all  the  functions  of  the  body."  Differing  from  Crile, 
he  quite  justly  questions  the  legitimacy  of  distinguishing  etiologically 
between  shock  and  collapse.  He  fails,  however,  to  give  satisfactory  proof 
of  his  theory  of  shock. 

4.  Deficiency  of  Carbon  Dioxide  in  the  Blood  or  Acapnia. — Henderson 
thought  that  shock  was  due  to  a  deficiency  of  carbon  dioxide  in  the  blood 
on  account  of  the  rapid  and  deep  breathing  induced  by  traumatism,  so 
causing  an  undue  ventilation  of  the  lungs  resulting  in  a  condition  of 
overoxygenation  of  the  blood  with  diminished  carbon  dioxide  or  acapnia. 
Carbon  dioxide  is  not  merely  a  poisonous  excretion,  but  is  an  important 
regulator)'  hormone  upon  whose  presence  depends  the  activity  of  the 
respiratory  centers.  According  to  Henderson  the  tonicity  of  the  walls 
of  the  bloodvessels  is  in  direct  proportion  to  the  carbon  dioxide  content 
of  the  blood. 

This  doctrine  of  acapnia  is  clinically  untenable,  as  in  the  great  major- 
it)'  of  cases  of  shock  excessive  ventilation  of  the  lungs  cannot  be  regarded 
as  a  causative  factor.  Howell  demonstrated  that  the  heart  still  beats 
in  complete  acapnia,  and  Seelig  found  that  by  introducing  directly 
carbon  dioxide  into  the  blood  current,  he  could  not  influence  the  course 
of  shock. 

5.  Morphological  Changes  in  the  Ganglion  Cells.  G.  W.  Crile  explains 
shock  by  the  exhaustion  theory.  According  to  him,  the  brain  is  a  great 
storage  batten  in  the  kinetic  system,  driving  the  suprarenal,  the  muscles, 
and  through  its  action  on  the  suprarenal,  the  other  important  viscera. 
In  his  judgment  all  forms  of  shock  are  caused  by  overstimulation 
of  the  nervous  system,  and  finally  by  exhaustion.  Basing  his  theory 
upon  stud)-  of  the  phylogenetic  history  of  the  whole  motor  mechanism, 
he  claimed  that  when  there  is  no  response  to  nervous  stimulation,  the 
energy  is  expended  in  the  cortical  cells.  The  brain  cells  then  show 
physical  changes  which  vary  with  the  stage  of  shock  in  which  they  are 


512  POSTOPERATIVE  COMPLICATIONS 

examined.  He  found  in  the  brain  cells  hyperchromatic  stages  followed 
by  hypochromatic  ones.  In  his  judgment  these  demonstrable,  constant 
morphological  alterations  of  the  brain  cells  are  the  primary  cause  of  shock. 
This,  he  thinks,  he  has  been  able  to  demonstrate  by  an  enormous  amount 
of  experimental  work  done  in  the  numerous  and  various  states  and  con- 
ditions. The  brain  cells  studied  were  almost  entirely  those  of  the  cere- 
bellum (Purkinje  cells).  As  Seelig  says,  "the  essence  of  his  doctrine  lies 
in  the  belief  that  the  cells  are  composed  of  labile  compounds  capable, 
when  adequately  stimulated,  of  converting  their  potential  energy  into 
kinetic.  If  this  power  to  convert  is  unduly  excited,  phenomena  of 
exhaustion  with  all  their  consequences  occur." 

Gray  and  Parson,  two  English  authors  who  have  worked  along  the 
same  line  as  Crile,  most  definitely  and  emphatically  state  that  the  most 
careful  histological  examination  of  the  brains  and  spinal  cords  of  shocked 
animals  fails  to  reveal  any  changes  in  the  ganglion  cells  as  described  by 
Crile  and  Dolly.  In  the  spinal  cords  they  found  no  cytolytic  changes 
whatever.  The  spinal  cortex  showed  very  little  change  and  the  Purkinje 
cells  showed  no  striking  alterations.  They  concluded  that  in  shock  the 
exhaustion  theory  cannot  be  proved  histologically. 

Mann  claims  that  it  is  impossible  to  reduce  the  anesthetized  animal 
to  a  state  of  shock  by  any  degree  of  sensory  stimulation,  provided  all 
hemorrhage  is  prevented  and  its  abdomen  not  opened. 

Since  the  same  pathological  changes  as  the  ones  described  by  Crile 
are  found  in  other  conditions  than  shock,  as  overwork,  anemia,  infection, 
poisoning,  Graves'  disease,  etc.,  these  changes  are  not  in  the  least  con- 
sidered by  many  as  specific  of  any  etiological  factor,  nor  are  they  specific 
for  shock.  Seelig  says,  "The  theory  of  ganglion-cell  excitation  as  the 
primary  cause  of  shock  stands  as  the  type  of  sohdistic  pathology. 
Virchow  has  characterized  all  sohdistic  theories  in  pathology  (as  con- 
trasted with  humoral  theories)  as  metaphysical  and  speculative;  and  in 
this  statement  resides  the  crux  of  the  problem.  Crile  may  encounter 
no  difficulty  in  showing  that  the  condition  of  shock  has  definite  morpho- 
logical representation  in  the  ganglion  cells  of  the  cerebellum,  but  he 
frequently  approaches  dangerously  near  the  borderline  of  speculative 
metaphysical  reasoning  in  his  attempt  to  prove  that  these  same  morpho- 
logical changes  are  the  primary  cause  of  shock." 

6.  Loss  of  Vasomotor  Control. — Janeway  and  Ewing  claim  that  shock 
is  due  to  loss  of  vasomotor  control  caused  by  inhibition  from  afferent 
sensory  impulses.  To  prove  their  contention  they  have  undertaken  a 
series  of  very  interesting  experiments.  But  through  what  mechanism 
this  condition  is  brought  about  is  not  explained  by  them. 

7.  Primary  Suprarenal  Exhaustion. — Finally,  the  last  theory  of  shock 
up    to    date    is    the    one    of    Corbett:    primary    suprarenal    exhaustion 


PRIMARY  SUPRA  REX A L  EXHAUSTION  513 

is  a  shock  factor.  Corbett  says:  (he.  cit.)  "The  amount  of  epinephrin 
in  the  blood  of  a  normal  individual  is  very  slight,  somewhere 
between  one  part  in  two  hundred  millions,  as  determined  by  Hoskins, 
and  one  part  in  ten  millions  as  determined  by  Waterman  and 
Smith.  Further  than  this,  the  epinephrin  output  per  minute  per 
kilogram  of  dog  cannot  be  above  0.2  c.c.  of  a  1  :  1,000,000  solution 
of  epinephrin.  The  smallest  amount  of  epinephrin  that  will  have 
anv  effect  upon  the  blood-pressure  ol  a  normal  dog  is  0.42  c.c.  of 
the  same  solution.  This  amount  produces  not  a  rise,  but  a  fall  in  the 
blood-pressure,  and  the  amount  necessary  to  produce  a  rise  is  several 
times  as  much.  These  facts  indicate  that  in  the  normal  individual  just 
enough  epinephrin  is  in  circulation  to  maintain  the  tone  of  the  'myo- 
neural junction,'  as  the  pegs  of  a  violin  maintain  the  tension  of  the 
strings.  Therefore  we  have  no  right  to  say  that  the  normal  blood- 
pressure  is  maintained  by  epinephrin  in  the  blood,  but  rather  that 
epinephrin  sensitizes  unstriped  muscles  of  the  vasomotor  system  to  the 
sympathetic.'1'' 

Furthermore,  the  splanchnic  nerves  must  also  be  intact  in  order  to 
have  function  of  the  suprarenal  glands,  as  shown  by  Cannon,  Dreyer 
and  Elliot.  Peritoneal  traumatism,  stimulation  of  the  sciatic  as  shown 
by  Elliot,  reduce  not  only  the  epinephrin  output,  but  also  actually 
reduces  the  epinephrin  content  of  the  glands.  After  a  number  of  experi- 
ments Corbett  comes  to  the  conclusion  that  symptoms  of  shock  fully 
develop  onlv  after  the  supplv  of  epinephrin  is  greatly  depleted.  Epi- 
nephrin exhaustion  is  a  shock  factor. 

Such  are  the  theories.  Everyone  of  them  sees  a  part  of  the  truth, 
but  none  of  them  explains  the  problem  of  shock  full)*.  Shock  is  a  com- 
posite of  various  factors.  It  seems  to  me,  however,  that  Crile  is  on  the 
right  track,  when  he  requires  for  the  production  of  shock  the  interven- 
tion of  the  nervous  sytem,  whatever  form  it  may  take,  but  takes  things 
too  much  for  granted  when  he  concludes  that  the  morphological  changes 
in  nervous  cells  are  the  primary  cause  of  shock.  How  far  have  we  the 
right  to  take  the  cells'  morphology  as  an  index  of  their  functional 
activity  :  Most  probably  in  the  course  of  future  researches  and  when  our 
knowledge  of  biological  chemistry  is  more  advanced,  we  may  find  the 
solution  of  the  problem  in  the  pathological  biologicochemical  interrela- 
tions not  only  of  the  nervous  system,  but  also  of  the  entire  apparatus 
of  internal  secretion.  What  would  tend  to  prove  that  my  contentions 
are  correct,  is  the  fact  that  shock  can  be-  nearly  always  successfully 
handled  if  a  sufficient  amount  of  new  blood  is  transfused.  I  his  has  been 
elegantly  shown  by  Janeway  and  Ewing.  I  hese  authors  saw  dogs,  so 
deeply  shocked  that  the  controls  similarly  shocked  died,  immediate!) 
resuscitated  by  blood  transfusion.  Why  should  it  be  so  if  the  primary 
33 


514  POSTOPERATIVE  COMPLICATIONS 

cause  of  shock  is  to  be  found  in  the  morphological  lesions  of  the  nervous 
system  ?  So  rapid  a  recovery  precludes  the  idea  that  the  disturbing 
factor  is  due  to  an  exhaustion  of  the  nerve  centers.  It  is  hard  to  con- 
ceive an  exhausted  center  recovering  so  quickly.  It  seems  reasonable 
to  admit  that  the  new  blood  transfusion  brings  "something"  which  is 
no  longer,  or  which  is  insufficiently  present,  in  the  system  of  the  shocked 
animal,  and  which  when  reintroduced  into  the  organism,  sets  going  all 
the  machinery,  just  as  a  few  drops  of  HC1  will  set  going  again  an  exhausted 
electric  battery.  What  this  something  can  be,  I  know  not.  Perhaps  as 
Corbett  says,  the  epinephrin;  perhaps  a  glandular  secretion  of  some 
other  sort,  or  one  or  more  lipoids,  or  one  or  more  biologicochemical 
compounds,  whose  chief  duty  is  to  stimulate  the  nervous  centers,  or 
possibly  some  others  of  the  organs  of  internal  secretion.  Not  enough 
attention  so  far  has  been  paid  to  the  organs  of  internal  secretion,  as 
to  their  possible  etiological  relation  to  shock. 

We  know  that  these  organs  contain  a  great  number  of  lipoids,  each 
one  of  them  possessing  individual  physiological  properties.  Certainly 
lipoids  must  not  be  the.  only  compounds  which  intervene  in  the  compli- 
cated biological  chemistry  of  our  body;  there  are  and  must  be  others, 
and  most  probably  it  will  be  only  when  we  know  more  of  the  science, 
still  in  its  infancy,  namely,  biological  chemistry,  that  we  shall  get  a  little 
nearer  the  solution  of  the  problem  of  shock. 

Shock  may  be  of  psychic,  traumatic,  toxic,  and  hemorrhagic  origin. 

It  is  quite  certain  from  clinical  observations  that  shock  may  follow 
psychic  disturbances  without  any  definite  trauma,  toxin,  and  loss  of 
blood.  This  psychic  shock  is  mostly  caused  by  fear  and  anxiety.  This 
psychic  factor  is  a  very  important  one,  and  it  is  often  not  given  sufficient 
consideration.  It  vanes  with  the  individual,  with  sex,  with  age,  race, 
and  social  condition.  The  fear  of  an  impending  operation  is  sometimes 
considerable,  and  it  is  indeed  the  duty  of  the  physician  and  surgeon  to 
alleviate  this  fear  as  much  as  possible. 

Traumatic  shock  in  accidental  injuries  has  been  known  for  many 
years.  Shock  connected  with  operation  seems  to  recognize  the  same 
causes  as  the  ones  seen  in  accidental  injuries.  For  a  long  time  surgeons 
have  felt  that  if  the  patient  is  generally  anesthetized,  the  operative 
manipulations  on  the  unconscious  patient  may  be  done  with  impunity. 
Crile  has  taken  the  opposite  stand  and  claims  that  even  during  artificial 
sleep,  painful  impulses  from  the  wound  to  the  brain  are  taking  place, 
are  registered  there  just  the  same,  but  are  not  felt,  as  the  entire  sensitive 
apparatus  is  anesthetized.  These  nocuous  impulses,  he  says,  are  a 
contributory  factor  of  shock;  they  increase  the  probability  of  post- 
operative complications,  increase  the  discomforts  of  the  convalescence 
and  prolong  the  period  of  disability,  and  they  should  consequently  be 


TREATMENT  OF  SHOCK  AXD  HEMORRHAGE  515 

eliminated  as  much  as  possible.  Hence  the  origin  of  the  anoci-associa- 
tion theory  of  Crile.  He  aims  to  prevent  shock  by  sequestering  the  brain 
from  the  field  of  operation  by  blocking  the  nerves  with  novocain.  I 
have  expressed  elsewhere  my  views  on  this  subject. 

Toxic  shock  may  be  seen  in  diseases  of  long  standing,  as  thvrotoxi- 
cosis,  typhoid,  acute  and  intestinal  obstruction,  jaundice,  certain  stages 
of  diabetes,  etc.  It  is  seen,  too,  after  the  use  of  drugs  for  local  and 
general  anesthesia. 

Hemorrhagic  shock  is  seen  after  severe  hemorrhages  either  previous, 
during,  or  after  operation.  Man)"  or  all  of  these  different  factors,  as  a 
rule,  are  combined  in  order  to  produce  shock.  One  factor  seldom  acts 
alone. 

Treatment  of  Shock  and  Hemorrhage. — Prevention  is,  of  course,  the 
best  method  of  treatment.  It  is  clear  that  if  it  is  true  that  during  gen- 
eral anesthesia,  nocuous  impulses  are  nevertheless  transmitted  to  the 
brain  in  such  a  way  as  to  jeopardize  the  life  of  the  patient,  something 
should  be  done  to  prevent  that  risk.  Consequently,  if  one  believes  in 
Crile's  theory  of  shock  and  in  his  anoci-association  theory,  to  be  con- 
sistent with  himself,  he  will  have  to  employ  the  methods  which  Crile 
advocates  in  order  to  prevent  shock.  I  have  done  so  for  three  years. 
But,  as  said  before,  since  this  present  war  broke  out,  as  novocain  could 
not  be  had  any  longer,  I  felt  forced  to  give  up  the  anoci-association 
method.  Despite  that  fact  I  have  been  unable  to  see  anv  difference 
for  the  worse  in  my  results.  So,  until  further  convincing  proof,  I  have 
discarded  the  use  of  novocain. 

The  necessity  of  eliminating  as  much  as  possible  the  factor  of  fear 
is  self-evident  and  this  can  be  done  by  the  most  careful  cooperation  on 
the  part  of  the  nursing  and  operating  staff.  It  may  be  reduced  to  a 
great  extent,  too,  by  the  intelligent  use  of  morphin  or  pantopon.  As 
claimed  by  Crile,  general  anesthesia  should  be  administered  very  care- 
fully, taking  care  to  prevent  loss  of  body  heat,  and  to  avoid  hemorrhage 
during  operation;  furthermore,  the  tissues  should  be  handled  carefully, 
without  roughness,  and  the  operation  should  be  performed  with  such 
speed  as  is  commensurate  with  the  safety  of  the  patient. 

It  would  be  an  error,  however,  to  believe  that  because  one  has  blocked 
the  nerves,  has  eliminated  the  factor  of  fear,  has  used  nitrous  oxide, 
etc.,  in  short,  has  applied  the  method  of  anoci-association,  that  he  is 
safe  in  undertaking  any  operation  on  a  patient,  and  that  he  may  be 
sure  that  the  outcome  will  be  all  right.  This,  indeed,  is  not  so.  The 
best  anoci-association  method  I  know  of  is  a  sound  surgical  judgment. 
As  already  said  more  than  once,  the  judgment  and  experience  <>t  the 
surgeon  will,  1  think,  determine  very  largely  the  outcome  of  each  given 
case.    \\  c  have  killed  a  great  many  patients  with  exophthalmic  and  other 


516  POSTOPERATIVE  COMPLICATIONS 

forms  of  goiter  because  we  have  done  too  much,  because  we  have  used 
a  general  anesthesia  when  local  anesthesia  should  have  been  used, 
because  we  have  subjected  them  to  an  operation  near  or  at  the  top  of  a 
wave  of  hyperthyroidism,  because,  in  other  words,  we  have  done  "  the 
right  thing  at  the  wrong  time,  or  the  wrong  thing  at  the  right  time." 
There  is  possibly  no  other  field  in  surgery  where  it  is  truer  than  in  thy- 
roid surgery  that  the  surgeon  must  be,  not  only  a  good  technician,  but 
also  a  most  capable  physician,  competent  to  appreciate  the  strength  of 
the  heart,  to  judge  how  much  shock  a  nervous  system  will  stand  and 
how  much  it  will  not,  to  know  if  the  case  is  complicated  with  thymus 
enlargement  or  not,  and  to  decide  if  the  degenerative  processes  of  the 
organs  have  gone  so  far  as  to  compromise  the  success  of  the  operation, 
or  if  they  will  stand  the  strain.  Even  with  the  best  medicosurgical 
judgment  and  with  wide  experience  every  surgeon  will  meet  with  mis- 
fortunes because  the  conditions  found  are  very  deceiving.  A  heart 
seems  to  respond  beautifully  to  a  preliminary  treatment,  and  great  is 
the  disappointment  when  you  expect  this  heart  to  stand  by  you,  to  find 
that  it  simply  "quits."  That  is  why  I  believe  Crile  is  not  doing  himself 
justice,  and  is  giving  too  much  credit  to  his  anoci-association  theory, 
when  he  attributes  the  good  results  mostly  to  this  method.  Ten,  five, 
yes,  even  two  years  ago,  the  technic,  the  indications,  the  conception  of 
the  operations,  were  not  in  many  respects  what  they  are  today,  and 
very  likely  in  a  few  years  from  now  they  will  have  advanced  and 
changed  again.  Our  experience  becomes  every  day  larger,  and  with  it 
improves  our  surgical  judgment.  Every  day  we  learn  better  what  to 
do,  what  not  to  do,  how  far  to  go,  and  how  far  not  to  go.  How  could 
it  be  otherwise?  If  we  consider  the  results  of  the  men  of  great  authority, 
such  as  Kocher  and  Mayo,  who  do  not  apply  the  method  of  anoci- 
association  as  advocated  by  Crile,  and  who  do  not  use  nitrous  oxide, 
we  see  that  their  results  are  not  only  among  the  best,  but  are  also  con- 
stantly improving.  What  shall  we  say  of  Kocher,  who  systematically 
uses  local  anesthesia  in  his  goiter  work,  who  does  not  make  a  point  of 
eliminating  the  factor  of  fear,  whose  patients  know  beforehand  the  day 
and  the  very  hour  of  their  operation,  and  who  even  walk  to  the  operating 
table?  Everyone  of  us  knows  that  an  operation  performed  under  local 
anesthesia  is  not  as  painless  as  one  would  wish  it,  consequently  the 
nocuous  impulses  toward  the  brain  are  still  extremely  active  and  harm- 
ful, yet  who  can  criticise  Kocher's  results,  not  only  so  far  as  mortality, 
but  so  far  as  immediate  and  remote  results  are  concerned.  I  think  Bevan 
is  quite  correct  when  he  says:  "Cnle's  excellent  surgical  work  is  done 
not  because  of  anoci-association,  but  in  spite  of  it." 

When  shock  takes  place  during  the  operation,  the  anesthetic  should 
be  stopped  at  once,  and  the    operation    interrupted    if   possible.     Then 


6 

0 

i 

0 

o 

3 

60 

0 

So 

0 

20 

0 

TREATMENT  OF  SHOCK  AXD  HEMORRHAGE  517 

if  a  two-staged  operation  can  be  devised,  it  is  far  better  to  do  so. 
If  not,  as  much  as  possible  of  the  operation  must  be  done  under  local 
anesthesia. 

When  shock  is  already  established,  it  is  treated  in  the  following 
manner:  the  extremities  are  bandaged;  the  foot  of  the  bed  or  operating 
table  is  elevated;  heat  is  applied  if  the  patient  is  cold;  ice  to  the  head  in 
hot  weather,  or  if  the  patient  has  temperature.  If  tachycardia  is  very 
marked  an  ice-bag  is  applied  to  the  cardiac  region.  If  the  patient  is 
very  restless,  small  doses  of  morphin  may  be  given  with  benefit.  If 
shock  is  only  moderate,  proctoclysis  by  the  drop  method  with  the 
following  solution  should  be  started  at  once. 

Sodium  chloride 

Calcium  chloride 

Potassium  chloride 

Bicarbonate  of  soda 

Glucose 

Alcohol      

Aq.  dest 1000. o 

This  should  not  be  given  in  too  great  quantities  at  a  time,  but  should 
be  repeated  at  intervals,  and  given  slowly.  This  solution  increases  the 
pressure  in  the  vena  cava,  and  since  the  output  of  the  heart  is  in  direct 
proportion  to  the  pressure  in  the  vena  cava  and  not  at  all  to  the  aortic 
pressure,  rectal  infusions  at  once  increase  the  blood-pressure  and  the 
volume  of  the  pulse. 

Hypodermoclysis  is  best  made  underneath  the  breast  or  in  the  axilla. 
If  for  any  reason  the  thorax  must  be  avoided,  the  space  of  Retzius  can 
be  used  advantageously. 

If,  however,  one  is  in  need  of  more  quickly  acting  methods, 
intravenous  infusion  must  be  resorted  to  at  once.  The  best  solution 
to  use  is  the  Locke-Ringer,  which  is  far  superior  to  the  salt  solution 
commonly  used  up  to  date.  The  Locke  solution  has  been  employed 
for  a  number  of  years  in  laboratories  not  only  as  a  means  of  keeping 
up  artificial  circulation  in  experimental  work,  but  also  as  a  medium 
to  preserve  the  life  and  excitability  of  the  tissues  coming  from  the  liver, 
intestines,  urether,  etc.     Its  composition  is  the  following: 

Sodium  chloride 8.0  "rams 


Calcium  chloride  (non-crystal 


(if  crystallized) 0.4 


Potassium  chloride   . 
Bicarbonate  of  soda 
I  )extrose  I  purified)  . 

\<|.  desi 

<  K\  gen,  1  nough  to  saturate. 


zed) o. 


•ram 


0.2      " 

0.2      " 

1.0      " 

1000.0  c.c. 


518  POSTOPERATIVE  COMPLICATIONS 

The  Locke  solution  is  preserved  in  sterile  bottles  and  the  whole 
sterilized  anew  at  the  autoclave.  The  chemical  products  entering  into 
the  formula  must  be  chemically  pure.  The  oxygen  which  is  a  necessary 
condition  for  experimental  work  when  producing  artificial  circulation,  is 
no  longer  necessary  when  used  clinically  for  transfusion. 

The  sodium  chloride  is  used  in  order  to  give  the  liquid  the  osmotic 
property  equal  to  the  one  of  the  blood,  so  that  the  hemoglobin  will  remain 
fixed  to  the  red  corpuscles,  in  other  words,  m  order  to  prevent  hemoly- 
sis. The  calcium  is  necessary  to  keep  up  the  function  of  the  heart  and 
the  potassium  is  intended  to  regulate  the  function  of  the  cardiac  fibers. 
The  bicarbonate  of  soda  is  necessary  in  order  to  confer  to  the  liquid 
about  the  same  alkalinity  as  the  blood.  Glucose  is  destined  to  be  a 
nutritive  element  for  the  myocardium. 

Adrenalin  may  be  added  to  the  infusion  or  given  separately  hypo- 
dermically;  15  to  20  drops  of  a  1  :  1000  solution  is  an  excellent  stimu- 
lant. Strophantine  given  intravenously  is  sometimes  very  effective.  It 
is  found  on  the  market  in  sterile  ampules,  each  containing  1  c.c.  of  a 
1  :  1000  solution.  This  injection  may  be  repeated  six  to  ten  hours  after, 
but  generally  not  again.  Small  but  often-repeated  doses  of  strychnin 
are  also  of  good  value.  Alcohol  seems  to  have  but  little  effect.  When 
the  acute  stage  of  shock  is  over,  digalen,  given  hypodermically  or  intra- 
venously, proves  sometimes  an  excellent  stimulant. 

However,  the  best  of  all  methods  for  the  treatment  of  shock  is  blood 
transfusion;  it  may  be  done  by  the  direct  or  indirect  method.  The  indi- 
rect method,  however,  is  the  one  which  is  within  the  reach  of  everyone 
on  account  of  its  simplicity,  and  what  is  more,  it  is  just  as  effective  as 
the  method  of  direct  transfusion.  The  indirect  method  which  I  have 
devised  can  hardly  be  improved  in  its  simplicity. 

Crotti's  Technic  of  Indirect  Transfusion. — Although  thoroughly  familiar 
with  the  technic  of  vascular  surgery,  I  have  always  felt  that  the  direct 
transfusion  of  blood  by  arteriovenous  anastomosis  is  a  very  delicate 
operation  and  too  often  unsuccessful.  Everyone  who  is  familiar  with 
that  kind  of  work  knows  how  difficult  it  is  to  anastomose  properly  the 
small  vein  of  a  child,  for  instance,  with  the  large  radial  artery  of  a  man, 
and  even  when  the  anastomosis  has  been  successfully  performed,  there 
is  no  way  of  telling  whether  the  arterial  blood  is  running  into  the  vein, 
and  if  it  is,  how  much  has  been  transfused.  The  operation  is  a  long  and 
difficult  one.  The  same  objections  are  true  for  the  other  methods  of 
transfusion  as,  for  instance,  when  performed  with  small  glass  tubes 
prepared  with  albohne  or  paraffin.  Therefore  I  sought  to  find  a  simpler 
method  which  might  be  just  as  efficient,  if  not  more,  and  become  more 
popular  on  account  of  its  simplicity.  It  is  called  indirect  transfusion  of 
blood. 


POSTOPERATIVE  HYPERTHYROIDISM  519 

With  Dr.  Shilling,  pathologist  at  Grant  Hospital,  Columbus,  Ohio, 
I  made  a  series  of  experiments  on  dogs  in  order  to  determine  the  coagu- 
lation time  of  the  blood,  when  withdrawn,  first,  in  a  sterile  drv  glass; 
second,  in  a  glass  boiled  in  normal  salt  solution;  third,  in  a  glass  boiled  in 
alboline.  The  average  coagulation  time  was  from  five  to  eight  minutes  for 
blood  withdrawn  in  a  sterile  dry  glass,  and  from  seven  to  twelve  minutes 
for  blood  withdrawn  in  glass  boiled  in  salt  solution  or  alboline.  Therefore 
I  thought  there  would  be  plenty  of  time  to  withdraw  blood  with  a  svringe 
from  a  vein  and  to  reinject  it  into  another  one  without  running  any 
danger  of  coagulation.  This  was  indeed  successfully  demonstrated  in 
each  of  our  numerous  experiments.  We  were  able,  provided,  that  cer- 
tain rules  were  followed,  to  withdraw  several  hundred  centimeters  of 
blood  from  the  vein  of  a  dog  and  to  reinject  it  into  the  vein  of  another 
without  a  particle  of  trouble.  I  was  able  also  to  demonstrate  the 
efficacy  of  the  method  in  human  surgery  more  than  once. 

Iodin  preparation  of  the  skin  of  the  donor.  Local  anesthesia 
with  novocain,  I  per  cent.  Incision  of  the  skin  three  or  four  centi- 
meters long  in  the  angle  of  the  elbow.  The  cephalic  vein  is  dissected 
out  and  cut  at  the  upper  end  of  the  incision.  The  proximal  end  is  ligated 
with  catgut.  To  the  distal  end  three  small  mosquito  forceps  are  applied 
at  an  equal  distance  one  from  the  other  in  order  to  maintain  the  lumen 
of  the  vein  open.  A  small  artery  clamp  applied  a  fewT  centimeters 
below  prevents  the  blood  from  leaking. 

The  same  operation  is  performed  on  the  recipient  with  the  difference 
that  the  vein  is  ligated  at  the  lower  end  of  the  incision. 

A  blunt  needle  which  has  been  adapted  to  the  syringe  is  introduced 
into  the  vein  of  the  donor  in  the  opposite  direction  to  the  blood  current; 
blood  is  aspirated  into  the  syringe,  and  reinjected  into  the  vein  of  the 
recipient,  in  the  same  direction  as  the  blood  current. 

The  transfusion  may  be  repeated  as  often  as  is  necessary  without 
coagulation,  provided,  needle  and  syringe  are  freshly  washed  each  time 
with  a  warm  normal  salt  solution.  The  best  plan  is  to  have  two  needles 
and  two  syringes,  and  to  have  one  set  washed  by  the  assistant  while 
the  other  is  in  use.  When  transfusion  is  terminated  the  veins  are  ligated 
and  the  skin  incision  closed.  By  this  method  any  amount  of  blood  may 
be  transfused  from  one  patient  to  another,  and  the  exact  amount  trans- 
fused is  known.  1  he-  fact  that  the  blood  is  venous  seems  to  be  without 
importance.  1  he  technic  is  simplicity  itself  and  may  be  used  by  any- 
one.    A  few  bubbles  of  air  are  of  no  importance. 

If  one  prefers  to  take  arterial  blood  from  the  donor,  he  may  do  so 
by  preparing  the  radial  artery  in  the  same  way  as  described  above. 

Postoperative  Hyperthyroidism.  Whoever  has  operated  many  thy- 
rotoxic goiters  must   have  occasionally  met  with  this  dreaded  compli- 


520  POSTOPERATIVE  COMPLICATIONS 

cation.  Fortunately,  postoperative  hyperthyroidism  is  very  much  less 
frequent  today  than  it  was  in  the  early  period  of  thyroid  surgery 
because  of  our  better  knowledge,  better  technic,  and  better  judgment, 
nevertheless  this  complication  does  occur,  and  sometimes  very  unex- 
pectedly, no  matter  how  small  the  surgical  traumatism  has  been. 

Generally  speaking,  we  may  say  that  postoperative  hyperthyroidism 
is  only  an  exaggeration  of  all  the  symptoms  seen  in  Basedow's  patients. 
It  is  characterized  by  palpitation,  tachycardia,  tremor,  vomiting,  fever, 
sweating,  extreme  agitation,  hallucinations,  psychosis,  etc.  Though 
often  the  operation  is  not  yet  terminated,  the  tachycardia  is  already 
intense,  the  pulse  beating  between  150  and  200.  As  soon  as  the  patient 
comes  out  of  the  anesthetic  he  shows  extreme  agitation;  jumps  up  in 
his  bed;  his  whole  body  shaken  by  an  intense  tremor;  perspiration  is 
abundant,  and  although  there  is  no  mechanical  obstruction  in  the 
trachea,  the  patient  shows  air  hunger;  temperature  climbs  up  to  103 
or  1040  F.  or  more;  the  highest  I  have  seen  was  107 °  F.  The  patient 
becomes  more  and  more  restless,  wants  to  get  out  of  bed,  and  to  go  home; 
has  hallucinations;  sees  people,  and  talks  vehemently.  The  condition 
usually  reaches  its  most  acute  stage  toward  the  end  of  the  second  day. 
This  peracute  form  of  hyperthyroidism  lasts  one,  two  and  three  days 
and  usually  terminates  in  death.  In  the  milder  forms,  however,  the 
symptoms  are  less  pronounced:  the  storm,  less  intense,  is  over  sooner. 

The  nature  of  this  postoperative  hyperthyroidism  is  not  yet  clear. 
Rehn,  Mikulicz,  Moebius  and  others  believe  that  it  is  due  to  an  abun- 
dant resorption  of  thyroid  secretions  intensely  toxic.  This  may  be  true 
in  certain  number  of  cases  but  this  explanation  does  not  hold  good  for 
all  cases  since  Curtis  and  Delore  have  observed  it  after  sympathectomy, 
Pollosson  after  a  gynecological  operation  in  a  Basedow  patient,  and 
Crile,  after  only  "the  prick  of  a  hypodermic  needle."  Since  it  appears 
after  simple  ligation,  after  enucleation  or  resection,  no  matter  whether 
one  leaves  a  raw  surface  or  not,  it  would  appear  that  the  "raw  surface" 
and  "squeezed  juice"  hypothesis  do  not  adequately  explain  post- 
operative hyperthyroidism.  Kocher  and  Riedel  believe  that  hyperthy- 
roidism is  due  to  general  anesthesia.  This,  however,  is  not  always  true 
since  it  has  been  observed  after  the  use  of  local  anesthesia. 

It  cannot  be  denied,  however,  that  the  anesthetic,  no  matter  whether 
ether  or  nitrous  oxide  is  employed,  is  -per  se  a  potent  contributing  factor 
in  the  production  of  postoperative  hyperthyroidism.  Local  anesthesia 
is  far  less  liable  to  cause  postoperative  hyperthyroidism  than  general 
anesthesia. 

Crile  claims  that  postoperative  'hyperthyroidism  is  due  to  shock. 
Some  authors  think  that  postoperative  hyperthyroidism  is  related  to 
thymic  hyperplasia.     Most  likely    this  is  partly  true  since  the  thymus 


ACIDOSIS  521 

belongs  to  the  chain  of  organs  of  internal  secretion  and  inasmuch  as  that 
gland  plays,  as  we  shall  soon  see,  a  part  in  the  production  of  post- 
operative hyperthyroidism.  At  any  rate,  one  thing  m  my  practice  seems 
to  corroborate  these  views.  Since,  as  routine  work,  I  combine  thyroidec- 
tomy with  thymectomy,  postoperative  hyperthyroidism  is  far  less 
frequent  in  my  experience  than  it  used  to  be. 

In  my  judgment  postoperative  hyperthyroidism  is  nothing  more  nor 
less  than  a  fulminating  spell  of  the  ordinary  hyperthyroidism  which 
we  see  even'  day  in  thyrotoxic  patients.  The  symptoms  are  the  same. 
The  only  difference  is  a  matter  of  degree.  In  postoperative  hyperthy- 
roidism all  the  symptoms  are  greatly  intensified  sometimes  to  such  an 
extent  that  the  organism,  unable  to  stand  the  impact,  is  swept  away  in 
two  or  three  d.ays  by  this  tremendous  wave  of  hyperthyroidism.  Just 
as  in  an  ordinary  case  of  thyrotoxicosis,  shock,  be  it  psychic  or  traumatic, 
be  it  light  or  severe,  is  liable  to  determine  a  very  acute  spell  of  hyper- 
thyroidism, so  in  any  surgical  intervention,  be  it  ligation,  resection, 
gynecological  operation,  or  only  the  pricking  of  a  needle  as  in  Crile's 
case,  the  traumatic  shock  from  the  operation,  the  psychic  shock  from 
going  through  the  ordeal,  and  the  toxic  shock  from  the  use  of  the  anes- 
thetic, etc.,  are  all  factors  which,  with  others,  intervene  in  producing  the 
thyrotoxic  explosion  called  postoperative  hyperthyroidism.  It  is  con- 
sequently logical  to  consider  postoperative  hyperthyroidism  and  ordi- 
nary hyperthyroidism  as  having  the  same  cause.  As  we  have  consid- 
ered the  latter,  a  thyro-neuro-polyglandular  disease,  so  we  consider 
the  former  as  a.  fulminating  thyro-neuro-polyglandular  spell.  The  organ- 
ism is  suddenly  flooded  with  an  enormous  amount  of  thyroid  products, 
be  it  from  overfunction  of  the  gland  or  from  absorption  from  the  "raw 
surface"  itself.  The  nervous  system  is  running  wild,  either  because 
driven  by  the  toxic  thyroid  products  or,  because  it  has  lost  its  "gyro- 
static  control,"  if  I  may  say  so.  The  polyglandular  system  is  working 
at  random,  thus  mobilizing  toxic  products  of  metabolism  which  only 
further  aggravate  the  situation.  In  short,  the  entire  thyro-neuro-poly- 
glandular machinery  is  out  of  gear. 

Acidosis.  Although  of  recent  acquisition,  acidosis  is  nevertheless  of 
vast  clinical  importance.  For  years  I  have  been  impressed  with  the  fre- 
quency with  which  the  "acetone  breath"  was  encountered  in  many  of 
my  postoperative-  casts.  I  thought  for  a  long  time  that  1  had  to  deal 
with  some  transitory  diabetes,  but  repeated  examinations,  however, 
failed  to  show  the  presence  of  sugar  in  the  urine.  In  [913  an  article  on 
the  subject  by  two  French  authors,  Chavain  and  Oeconomos  enlight- 
ened me  considerably,  as  they  showed  that  the  symptoms  which  I  had 
observed  were  due  to  acidosis.  Since  then  other  authors,  among  them 
Crile,  have  but  confirmed  their  views. 


522  POSTOPERATIVE  COMPLICATIONS 

Alkalinity  is  essential  to  life  not  only  for  animals,  but  for  plants 
also.  We  all  know  that  an  acid  soil  remains  non-productive  until  it 
has  been  alkalized  with  alkaline  fertilizers,  that  plants  cannot  grow  in 
acidulated  waters,  and  that  if  the  alkalinity  of  the  blood  in  animals 
becomes  lowered,  life  ceases.  All  the  fluids  of  the  body  except  the  urine 
and  gastric  juices  are  alkaline. 

Acid  is  constantly  being  formed  in  the  body  as  the  result  of  many 
metabolic  processes.  Exercise,  emotion,  etc.,  increase  the  amount  of 
acid  in  the  blood  which  in  turn  activates  the  respiratory  centers. 

One  of  the  most  characteristic  symptoms  of  acid  poisoning  is  an 
"acetone  breath;"  furthermore,  the  tongue  is  coated  or  perhaps  abnor- 
mally red,  the  face  is  pale,  or  sometimes  flushed,  the  surface  of  the  body 
is  often  cold  and  moist,  nausea  or  vomiting  may  be  present.  The  patient 
is  exceedingly  thirsty,  and  shows  excessive  nervous  irritability.  Acetone 
and  diacetic  acid  are  present  in  quantities  more  or  less  great  in  the 
urine. 

It  is  a  known  fact  that  starvation  is  a  great  source  of  acidosis  and 
that  in  a  surgical  case,  the  length  of  the  pre-  and  postoperative  starva- 
tion periods,  the  amount  of  anesthetic,  and  the  amount  of  surgical 
traumatism,  will  be  the  deciding  factors  in  the  intensity  of  acidosis. 

From  the  foregoing  facts  it  follows  that  we  ought  to  be  able  to  pre- 
vent, to  a  certain  extent  at  least,  acidosis  by  reducing  the  pre-  and  post- 
operative periods  of  starvation  to  a  minimum  and  by  reducing  the  amount 
of  anesthetic.  That  is  what  I  have  been  doing  as  a  general  principle  in 
my  surgical  work,  be  it  goiter  or  any  other  form  of  surgery.  I  do  not 
deplete  the  patient  any  more  with  cathartics:  when  a  cathartic  is  deemed 
necessary  it  is  given  several  days  before  the  operation.  Nor  do  I  restrict 
the  diet  of  my  patients  in  the  least  unless  there  should  be  a  special 
contra-indication  for  it;  on  the  contrary,  I  want  them  to  eat  plenty  of 
food;  even  their  last  meal  before  operation  must  be  a  good  substantial 
meal,  rich  in  carbohydrates.  In  severe  cases  where  I  fear  the  operation 
will  precipitate  an  impending  acidosis,  I  have  my  patients  take  some 
food  just  an  hour  or  two  before  the  operation,  as  oatmeal,  etc.  As  soon 
as  the  operation  is  over  and  as  soon  as  they  have  recovered  from  the 
anesthetic,  I  want  them  to  take  plenty  of  water  because  just  as  the 
acid  soil  needs  water,  so  does  the  acid  animal  body.  Even  if  they  vomit, 
water  is  still  given  plentifully,  at  least  for  a  time,  as  it  is  a  very  simple 
and  efficient  means  to  clean  out  the  stomach. 

It  may  seem  excessive  to  compel  patients  who  may  be  vomiting  to 
swallow  food,  yet,  in  severe  cases  a  few  hours  after  operation  as  soon  as 
the  stomach  has  sufficiently  quieted  down,  a  carbohydrate  food,  as  gruel, 
potato  soup,  etc.,  is  given  to  the  patient,  and  as  soon  as  possible  feeding 
is  pushed  to  the  limit. 


POSTOPERATIVE  FEVER  523 

Glucose  and  bicarbonate  of  soda  are  used  freely  before  and  after  the 
operation.  A  day  or  two  before  the  operation  the  patient  is  given  150 
grams  of  glucose  in  water  flavored  with  peppermint  which  renders  the 
taste  of  the  mixture  agreeable.  At  the  same  time  the  patient  is  given 
5  to  10  grams  of  bicarbonate  of  soda  daily.  As  soon  as  the  patient 
has  come  back  from  the  operating  room  a  proctoclysis,  20  to  25  drops  a 
minute,  is  started.     The  following  formula  is  used: 

Sodium  chloride 6.0  grams 

Calcium  chloride 1.0  " 

Potassium  chloride 0.3  " 

Bicarbonate  of  soda 100. o  " 

Glucose     150.0  " 

Alcohol 20.0  " 

Aq.  dest 1000. o  " 

If  the  acidosis  should  become  threatening  a  pint  or  two  ot  the 
following  solution  is  given  intravenously : 

Sodium  chloride 8.0  grams 

Calcium  chloride  (non-crystallized) 0.2  " 

(if  crystallized) 0.4  " 

Potassium  chloride 0.2  " 

Bicarbonate  of  soda 0.2  " 

Glucose 1 .0  " 

Aq.  dest 1000. o  c.c. 

At  the  same  time  bicarbonate  of  soda  is  given  larga  manu,  that  is, 
generously  by  every  possible  way. 

Postoperative  Fever. — Postoperative  fever  may  be  caused  by  infec- 
tion, or  may  be  entirely  independent  of  it. 

In  the  preaseptic  era  infection  was  one  of  the  most  feared  complica- 
tions. It  occurred  after  enucleation  or  after  resection,  and  too  often 
terminated  by  mediastinitis,  empyema,  and  pericarditis,  and  finally  by 
death.  But  in  these  daws  with  conscientious  and  intelligent  asepsis, 
with  careful  protection  of  the  field  of  operation  from  surrounding  parts, 
with  the  Kocher  screen,  and  with  carefully  selected  and  sterilized  suture 
material,  infection  is  very  rare;  in  fact,  it  seldom  occurs.  For  three 
years  consecutively  I  have  not  had  a  single  infection. 

There  is,  however,  another  form  of  postoperative  fever  which  is  not 
due  to  infection.  It  occurs  the  same  day  of  the  operation  and  usually 
reaches  its  maximum  on  the  second  or  third  day  after  operation.  It 
oscillates  between  102°  and  103  °,  and  seldom  goes  above  1040  1*.  Excep- 
tionally, however,  it  may  go  higher;  the  highest  temperature  I  have 
seen  was  107  I.,  which  terminated  by  death.  In  ordinary  condi- 
tions this  temperature  lasts  three,  four  and  five  days  and  then  gradu- 
ally disappears.      It  is  accompanied   by  an  increased   pulse-rate,  and   In 


524  POSTOPERATIVE  COMPLICATIONS 

more  or  less  marked  symptoms  of  hyperthyroidism.  This  postoperative 
fever  occurs  both  in  simple  and  thyrotoxic  goiter,  but  it  is  far  more 
frequent  and  far  more  marked  in  the  latter  condition. 

The  pathogeny  of  the  postoperative  fever  is  the  same  as  that  of 
postoperative  hyperthyroidism. 

Postoperative  Tetany. — Tetany  was  very  frequent  at  the  time  when 
total  thyroidectomies  were  performed  and  when  the  technic  of  goiter 
operations  had  not  reached  the  state  of  development  which  it  has  today. 
Nowadays  postoperative  tetany  is  rare.  Kocher  saw  it  only  5  times 
in  his  last  1000  operations;  Mayo,  in  1200  operations,  saw  it  once; 
Frazier,  reporting  the  results  of  2000  operations  done  by  American  sur- 
geons, found  8  cases  of  tetany  reported,  3  of  them  being  fatal;  Boese  in 
410  cases,  operated  on  by  Hochenegg,  found  2  cases  of  tetany.  I  have 
seen  it  twice  in  my  surgical  practice.  Thyroidectomy  does  not  need 
to  be  total  in  order  to  produce  tetany.  The  removal  of  one  lobe  only 
is  sometimes  sufficient  to  cause  it.  The  reason  lies  in  the  fact 
that,  although  only  one  or  two  parathyroids  have  been  removed, 
the  parathyroids  of  the  other  side  are  either  insufficient  or  absent. 
Benjamins,  who  made  a  systematic  examination  of  goiters  removed  by 
operation,  found  that  in  many  instances  one  or  two,  or  even  three  para- 
thyroids had  been  removed  with  the  goiter.  Another  reason  why  tetany 
may  appear  sometimes  after  partial  thyroidectomy  is  that,  on  account 
of  abnormal  vascular  development,  the  small  artery  which  supplies 
the  little  parathyroid  glandules  is  destroyed,  causing  necrosis  of  the 
parathyroids,  and  hence  the  tetany.  Erdheim  made  thorough  seriated 
microscopic  examinations  of  the  cervical  region  in  3  cases  which  died  of 
tetany.  In  the  first  case  he  found  no  trace  of  parathyroids,  but  found 
two  very  small  accessory  parathyroids  imbedded  in  the  thymus;  in  the 
second  case  only  one  parathyroid  was  found  but  it  was  entirely  necrotic; 
in  the  third  case  no  trace  of  parathyroid  tissue  could  be  found.  (See 
chapter  on  Parathyroids,  page  445.) 

Symptoms. — The  symptoms  of  postoperative  tetany  usually  appear 
in  the  next  twenty-four  hours  after  operation  and  are  characterized  at 
first  by  a  pricking  sensation  and  by  a  slight  stiffness  of  the  fingers.  The 
symptoms  usually  reach  their  maximum  on  the  third  day  and  are  always 
bilateral.  Exceptionally,  tetany  may  occur  only  six,  eight,  ten  or  fifteen 
days  after  the  operation.  Some  claim  that  it  may  even  happen  months 
or  years  after.  In  the  latter  cases  the  operation  cannot  be  held  directly 
responsible. 

When  fully  developed  the  disease  is  characterized  by  tonic  and  inter- 
mittent spasmodic  contractions  in  the  flexor  muscles  of  the  upper  extrem- 
ities. Such  contractions  are  present,  too,  but  in  a  lesser  degree  in  the 
lower   extremities.      The   interval   between   the   contractions   is   at   first 


POSTOPERATIVE  TETANY  525 

quite  marked,  but  gradually  they  become  more  intense  and  more  fre- 
quent. In  severe  cases  the  tonic  contractions  may  last  one  or  two 
hours;  m  such  conditions  the  musculature  of  the  back,  the  masseter 
muscles  and  the  diaphragm  may  become  involved.  Of  course  all  cases 
of  tetany  are  not  alike,  and  all  do  not  show  the  same  severity;  some  are 
of  the  mild  type  and  show  only  "tetanoid"  symptoms. 

Besides  the  muscular  contractions,  four  other  cardinal  symptoms  are 
found  in  tetany.      The}'  are: 

i.  The  Chvostek  symptom. 

2.  The  Weiss  symptom. 

3.  The  Trousseau  symptom. 

4.  The  Erb  symptom. 

The  Chvostek  symptom  is  a  sudden  and  fugacious  contraction  of  the 
muscles  of  the  face  obtained  by  a  slight  percussion  on  the  facial  nerve 
at  its  point  of  emergence  in  the  parotid  region.  Percussion  mav  be 
done  with  the  percussion  hammer  or  simply  with  the  finger  just  as  in 
the  act  of  percussing  the  thorax.  Percussion  must  be  very  gentle  and 
soft. 

Frankl-Hochwart  distinguished  three  different  degrees  of  the  Chvostek 
symptom : 

Chvostek  I. — The  entire  facial  musculature  of  the  side  percussed 
responds  to  a  slight  percussion  made  upon  the  facial  nerve  at  its  point 
of  emergence  in  the  parotid  region. 

Chvostek  II. — Contractions  are  localized  only  in  the  ala  nasi. 

Chvostek  III. — Contractions  are  seen  only  at  the  angle  of  the  mouth. 

The  Chvostek  symptom  has  been  considered  for  a  long  time  as  path- 
ognomonic of  tetany,  but  it  occurs  also  in  conditions  which  are  entirely 
foreign  to  parathyroid  insufficiency.  For  instance,  the  Chvostek  III 
may  be  found  in  tuberculosis,  epilepsy,  neurasthenia,  and  even  in  nor- 
mal individuals.  In  interpreting  the  Chvostek  III  one  should  be  sure 
that  it  is  not  of  muscular  origin,  because  sometimes  percussion  in  the 
outer  edge  of  the  orbicularis  oris  may  determine  some  fibrillar  contrac- 
tion in  that  muscle,  which  thus  becomes  a  source  of  error  of  interpreta- 
tion. On  the  other  hand,  the  Chvostek  may  be  missing  in  very  marked 
cases  of  true  tetany.  It  is  more  often  present  in  stomach  retain  of 
adults  than  in  infantile  tetany. 

I  lit  Weiss  symptom  is  a  sudden  contraction  of  the  muscles  frontalis 
corrugator  supercilu  and  orbicularis  oculi,  taking  place  when  the  tem- 
poral and  zygomatic  branches  of  the  facial  nerve  are  percussed  at  the 
outer  angle  of  the  orbita. 

I  he  Chvostek  and  Weiss  svmptoms  are  caused  by  an  exaggerated 
excitability  of  the  facial  nerve,  often  causing  the  entire  facial  musculature 
to  assume  a  peculiar  expression  known  as  the  "tetanic  face"     Fig.  88). 


526 


POSTOPERA  TI VE  COM  PLICA  TIOXS 


In  that  condition  the  angles  of  the  mouth  are  drawn;  the  nasolabial 
groove  is  more  deeply  marked,  and  there  is  an  anxious  expression  over 
the  forehead  with  the  eyelids  remaining  wide  open. 

The  Trousseau  Symptom. — In  1864  Trousseau  saw  that  by  exerting 
a  circular  compression  on  the  upper  arm  of  patients  with  parathyroid 
insufficiency,  so  as  to  compress  the  nerves  and  bloodvessels  in  the 
bicipital  groove,  spasmodic  contractions  and  flexion  of  the  forearm  and 
wrist  took  place.  At  the  same  time  the  hand  and  the  fingers  took  a 
position  known  since  as  the  accoucheur's  hand,  or  the  obstetrical  hand 
(Fig.  89).    The  best  way  to  produce  the  Trousseau  symptom  is  to  exert 


Fig. 


-Tetanic  face. 


circular  compression  on  the  arm  with  a  rubber  band.  Often,  however, 
simple  compression  with  the  two  hands  in  the  region  of  the  middle  arm 
is  sufficient.  The  Trousseau  symptom  may  appear  very  quickly  after 
circular  compression  has  been  started.  In  many  other  instances,  how- 
ever, compression  has  to  be  exerted  for  quite  a  long  time  before  the 
symptom  is  obtained.  In  some  cases  the  symptom  appears  only  after 
compression  has  been  removed. 

Where  the  Trousseau  symptom  is  fully  developed  and  the  accouch- 
eur's hand  is  present,  the  fingers  are  found  to  be  moderately  flexed  in 
their  phalangometacarpal  joints  but  extended  in  the  remaining  pha- 
langophalangeal  articulations.  The  thumb  is  in  middle  position  between 
adduction  and  opposition  and  tightly  closed  against  the  fingers  (Fig.  89); 
this  compression  may  be  so  intense  and  may  last  so  long  that  decubitus 
may  take  place  at  the  point  of  contact  of  the  thumb  with  the  fingers. 
The  hand,  as  a  rule,  shows  some  degree  of  palmar  flexion;  it  may  be, 


POSTOPERA  TI I  'E  TE TA  N I ' 


527 


however,  moderately  extended.  The  forearm  is  moderately  flexed  upon 
the  arm  and  in  the  middle  position  between  pronation  and  supination; 
at  the  same  time  it  is  adducted. 

In  the  lower  extremities  the  thighs  and  legs  are  extended;  the  feet 
show  a  plantar  flexion  of  the  toes  and  supination  of  the  foot.  The  posi- 
tion taken  by  the  foot  is  that  of  the  "equine"  or  "varoequine"  foot. 
Exceptionally,  the  foot  may  be  pronated  instead  of  supinated.  The 
adductor  muscles  of  the  thigh  being  spasmodically  contracted  bring 
consequently  the  thigh  into  marked  adduction.  Lately,  Schlesinger  has 
described  what  he  calls  the  "leg"  symptom.  The  leg  being  fully 
extended  on  the  thigh,  if  next  the  entire  limb  is  flexed  upon  the  pelvis, 
then,  after  two  or  three  minutes,  marked  tetanic  convulsions  appear  in 
the  limb. 


Fig.  89. —  letany.     "Accoucheur's"  hand. 


These  spasmodic  symptoms  found  in  the  upper  and  lower  extremi- 
ties, are  known  as  the  carpopedal  symptoms. 

The  tendinous  reflexes,  as  a  rule,  are  normal.  They  may  even  be 
slightly  diminished  especially  in  the  early  stages.  According  to  Falther 
and  Kahn  the  patient  after  a  severe  tetanic  spell  complains  of  pain  in 
the  bones  and  in  the  joints. 

Spasmodic  cramps  of  the  masseter  muscles,  of  the  tongue,  of  the 
diaphragm,  of  the  bladder  and  rectum,  arc  sometimes  observed  in  severe 
cases.  Spasmodic  contractions  of  the  esophagus  and  larynx  may  be 
present,  too.  Laryngospasm,  however,  is  more  frequently  seen  in 
infantile  tetany  than  in  that  of  postoperative.  Bechterew,  by  com- 
pressing the  phrenic  nerve,  caused  at  once  a  spasm  of  the  diaphragm. 


528  POSTOPERATIVE  COMPLICATIONS 

Intentional  cramps  are  not  so  infrequently  seen  in  postoperative 
tetany.  They  are  characterized  by  spasmodic  contractions  in  the  mus- 
culature which  for  a  few  seconds  may  prevent  the  patient  from  per- 
forming the  movements  which  he  had  intended  to  do;  for  instance,  if 
shaking  hands,  the  hand  remains  for  a  few  seconds  tightly  closed,  as  if 
the  patient  had  some  difficulty  in  releasing  his  grip.  Similar  intentional 
spasmodic  contractions  occur  in  the  lingual  and  esophageal  musculature. 

Frankl-Hochwart  has  shown  experimentally  that  the  Trousseau 
symptom  is  not  due  to  the  shutting  off  of  the  blood  circulation  in  the 
arm,  but  is  due  to  compression  of  the  nervous  trunks.  After  dissecting 
the  nerves  and  vessels  in  the  bicipital  groove  in  dogs,  this  author  was 
able  to  obtain  the  Trousseau  symptom  only  when  compressing  the 
nervous  trunks,  and  never  when  exerting  a  compression  upon  the 
arteries  and  veins  alone.  Pressure  upon  the  nervous  trunks  of  the  thigh 
gives,  too,  the  same  symptoms  which  have  been  described  above. 
According  to  Schlesinger,  if  compression  is  exerted  upon  purely  motor 
nerves  only,  no  Trousseau  symptom  occurs.  It  appears  only  in  mixed 
nerves,  namely,  those  containing  motor  and  sensory  fibers. 

The  Erb  Symptom.— In  1878  Erb  showed  that  in  tetany  the  elec- 
tric irritability  of  the  motor  nerves  was  gradually  increased.  This 
electric  excitability  is  higher  during  the  spasmodic  contraction  than 
during  the  intervals.  This  point  is  important  to  remember,  especially 
in  the  latent  forms  of  tetany  where  examination  may  show  that  during 
the  intervals  the  Erb  symptom  is  negative.  As  soon,  however,  as  the 
Trousseau  symptom  has  been  elicited,  the  Erb  symptom  becomes 
positive. 

The  hyperexcitabihty  of  the  nervous  trunks  is  best  determined  with 
the  galvanic  current.     It  is  characterized: 

1.  By  musculature  contractions  on  closure  of  the  negative  pole  with 
currents  of  intensity,  inferior  to  1  milliampere  when  this  current  is 
applied  on  the  ulnar  or  other  motor  nerves. 

2.  By  muscular  contractions  at  the  opening  of  the  positive  pole 
with  currents  inferior  to  5  milliamperes. 

3.  By  muscular  contractions  at  the  opening  of  the  negative  pole 
with  currents  inferior  to  5  milliamperes. 

Symptoms  of  hyperesthesia  are  frequently  found  in  connection  with 
tetany  and  are  especially  localized  in  the  upper  extremities.  They  con- 
sist of  a  burning,  pricking  sensation,  and  dead  feeling  of  the  fingers. 
Sensory  disturbances  of  the  hearing,  smelling,  tasting  apparatus  are  not 
so  uncommon.  The  pricking  and  tingling  sensations  are  sometimes 
intolerable. 

The  length  of  the  convulsions  may  be  very  short  or  may  last  for 
hours.     Sometimes  there  is  only  one  spasmodic  spell  and   then  every- 


POSTOPERATIVE  TETANY  529 

thing  is  over.  Usually,  however,  the  spells  are  numerous.  As  in  tetanus, 
noise,  touch,  light,  heat,  cold,  etc.,  may  determine  an  acute  spell.  Dur- 
ing convulsions,  the  muscles  are  hard,  offer  great  resistance  to  passive 
movements  and  are  spontaneously  painful.  Adrenalin  and  pilocarpin 
exaggerate  the  tetanic  contractions  and  determine  an  intense  vaso- 
constriction of  the  entire  bod}',  but  especially  of  the  face,  hence  the 
reason  why  patients  with  tetany  look  pale,  although  their  blood  is 
normal. 

Just  before  and  during  the  tetanic  cramps  there  is  tachycardia. 
The  heart  action  is  stronger,  the  sounds  are  more  strongly  marked, 
especially  the  second  pulmonary  and  aortic  sounds.  Respiration  is 
increased,  too.  Cyanosis  and  dyspnea  may  be  present.  The  respiratory 
disturbances  are  partly  due  to  spasmodic  convulsions  of  the  diaphragm, 
and  partly  to  disturbances  in  the  respiratory  centers.  As  a  rule  tem- 
perature does  not  go  very  high.  In  some  cases,  however,  it  may  be  very 
marked.     Even  vomiting  and  diarrhea  may  be  present. 

Tetany  should  not  be  mistaken  for  tetanus,  because  in  tetanus  the 
tendinous  reflexes  are  markedly  increased,  the  heart  is  not  involved,  and 
the  ordinary  symptoms  of  tetany  are  not  present. 

How  Many  Parathyroids  May  Be  Removed  Before  Tetany  Appears?  This 
question  cannot  be  fully  answered.  As  a  general  principle,  we  should 
aim  not  to  remove  any  parathyroid  tissue  at  all.  It  is  true  that  Erdheim 
found  that  one,  two,  or  even  three  parathyroids  had  been  removed  in  con- 
junction with  thyroidectomy  and  that  no,  or  very  little,  disturbance  was 
observed.  This  would  consequently  tend  to  prove  that  one  parathyroid 
alone  is  sufficient  to  prevent  tetany.  It  would  be  dangerous,  however, 
to  bank  too  much  upon  that  fact  since  we  know  that  not  only  the 
number,  but  also  the  size  of  the  parathyroids  are  two  important  factors 
in  the  production  or  non-production  of  parathyroid  insufficiency.  The 
volume  of  a  single  parathyroid  might  be  larger  than  that  of  three  other 
glandules  taken  together,  while  in  other  cases  two  small  parathyroids,  for 
example,  may  prove  insufficient  to  protect  the  patient  against  para- 
thyroid insufficiency.  Consequently  the  aim  of  the  surgeon  should  be  to 
protect  these  little  glandules  and  to  safeguard  them  from  any  injury. 

Despite,  however,  profound  anatomical  knowledge  and  good  technic, 
postoperative  tetany  will  sometimes  occur.  I  have  observed  a  case  of 
tetany  in  a  young  girl  whom  I  operated  for  a  nodular  colloid  goiter,  the 
size  of  a  small  egg,  located  in  the  isthmus.  This  median  goiter  was 
simply  enucleated.  Both  lobes  were  left  untouched  inasmuch  as  they 
were  normal.  No  ligation  of  the  thyroid  vessels  was  undertaken,  so  that 
I  cannot  see  how  I  might  have  injured  the  parathyroids,  yet  the  day 
following  the  operation  the  patient  developed  a  mild  case  of  tetany  which 
happily  was  cured  in  five  or  six  days  with  parathyroid  opotherapy  and 
$4 


530  POSTOPERATIVE  COMPLICATIONS 

lactate  of  calcium.  Tetany  in  this  case  does  not  necessarily  mean  that 
the  parathyroids  were  injured,  although  it  is  still  within  the  range  of 
possibilities  that  on  account  of  some  abnormal  anatomical  condition  a 
slight  injury  to  their  nervous  and  blood  supply  might  have  occurred, 
thus  putting  them  in  a  state  of  temporary  insufficiency.  It  is  more 
probable,  however,  that  for  some  reason  or  another,  they  had  been  tem- 
porarily inhibited  in  their  function.  Some  parathyroids,  like  some  other 
organs,  may  normally  have  a  reduced  functional  capacity;  they  may  be 
congenitally  weak,  too.  In  ordinary  conditions,  however,  they  are  still 
able  to  meet  the  physiological  requirements  of  the  metabolism,  since  their 
insufficiency  is  only  potential.  But  let  them  be  confronted  with  some 
abnormal  condition,  then  they  at  once  become  insufficient  to  their  task. 

Prognosis. — The  prognosis  of  postoperative  tetany  depends  upon 
the  quantity  of  parathyroid  tissue  left.  The  more  removed,  the  worse 
the  prognosis.  In  the  first  case  reported  by  Erdheim,  where  no  para- 
thyroid tissue  was  found,  death  occurred  three  days  after  accidental 
parathyroidectomy.  In  the  second  case,  where  the  one  parathyroid 
found  was  necrotic,  and  in  the  third  case,  where  two  tiny  para- 
thyroids were  found  imbedded  in  the  thymus,  death  occurred  seventeen 
days  after.  Most  probably,  in  the  two  latter  cases,  death  was  delayed 
on  account  of  some  partial  function  of  the  parathyroids  present.  If  the 
two  accessory  parathyroids  found  in  the  thymus  had  been  large  enough 
and  could  have  undergone  a  sufficient  compensatory  hypertrophy,  death 
very  likely  would  not  have  taken  place.  Most  likely,  some  of  the  cases 
of  chronic  tetany  which  we  sometimes  observe  can  be  explained  in  the 
same  way:  the  normal  parathyroids  for  some  reason  or  another,  having 
ceased  to  functionate  more  or  less  entirely,  the  accessory  parathyroids 
partially  supply  their  function  but  are  not  capable,  however,  of  offset- 
ting the  loss  of  the  main  parathyroids. 

The  course  of  tetany  in  experimental  pathology  is  the  same  as  the 
one  seen  in  human  beings.  The  disease  may  become  extremely  acute 
or  may  take  a  very  chronic,  slow  course.  Exacerbations  without  any 
apparent  cause  are  apt  to  be  observed.  In  animals  tetany  differs  materi- 
ally with  the  species  of  animal  involved.  For  instance,  dogs  develop  a 
markedly  acute  and  rapidly  fatal  tetany  after  complete  thyroidectomy, 
while  monkeys  show  a  more  chronic  form  of  the  disease.  In  human 
beings,  too,  we  observe  a  great  variety  in  the  form  and  intensity  of 
tetany.  From  the  most  severe  forms,  which  are  rapidly  fatal,  to  the 
lightest  form  of  the  disease,  all  stages  can  be  found.  Postoperative 
tetany,  no  matter  if  severe  or  light,  must  always  be  considered  as  a 
serious  complication,  since  we  know  that  even  the  lightest  form  of  tetany 
will,  for  no  apparent  reason,  suddenly  show  marked  exacerbations  which 
may   terminate  in   death.     Von   Eiselsberg  seems   to  think   that  when 


TREATMENT  OF   TETANY  531 

tetany  occurs  late,  that  is,  after  a  certain  period  of  time  after  opera- 
tion, its  prognosis  is  more  serious  than  in  cases  of  tetany  occurring  at 
an  earlier  period. 

Postoperative  tetany  may  retrocede  spontaneously  in  about  35  per 
cent,  of  the  cases.  When  death  takes  place  it  is  caused  by  spasm  of  the 
glottis,  of  the  diaphragm,  or  of  the  bronchi.  Postoperative  tetany  has 
a  great  tendency  to  become  chronic.  When  such  is  the  case  it  becomes  a 
troublesome  disease  since  it  is  hard  to  manage  by  therapeutic  treatment. 

Treatment  of  Tetany. — Opotherapy  with,  fresh  parathyroids  taken  from 
cattle  or  horses  has  proved  effective  in  a  great  many  instances.  Para- 
thyroids may  be  given,  too,  in  dry  form  either  in  powder  or  tablets. 
The  results,  no  matter  whether  the  parathyroids  are  taken  in  fresh  or 
dried  states,  have  not  always  been  satisfactory.  At  any  rate,  large 
doses  of  parathyroids  must  be  given  in  order  to  obtain  good  results. 

Having  observed  that  in  tetany,  elimination  of  calcium  is  enor- 
mously increased,  and  that  the  treatment  of  such  animals  with  calcium 
strontium  and  magnesium  diminishes  the  excitability  of  the  motor 
nerves  to  such  an  extent  that  the  spasmodic  contractions  disappear, 
MacCallum  and  Voegtlm  thought  that  tetany  was  due  to  a  poisonous 
substance  circulating  in  the  blood  and  depriving  the  tissues  of  their  cal- 
cium content.  They  consequently  advocated  the  use  of  calcium  in 
treating  parathyroid  insufficiency,  the  results  of  which  have  been  very 
satisfactory.  Other  authors  as  Parrhon,  Urechi,  Berkeley,  Beebe,  Bell, 
Martin,  Biedl,  have  confirmed  these  findings  and  results.  They  claim 
that  calcium,  strontium,  and  magnesium  act  directly  upon  the  nervous 
trunks  and  render  them  incapable  of  transmitting  the  nocuous  impulses 
causing  the  tetanic  convulsions.  Musser  was  able  to  check  tetany  in 
twenty-four  hours  after  administering  calcium  lactate  to  one  of  his 
cases.  Halstead,  while  treating  a  chronic  case  of  postoperative  tetany, 
replaced  the  parathyroid  opotherapy  by  lactate  of  calcium  and  obtained 
excellent  results.  Arthus  and  Schaefermann,  on  the  other  hand,  did 
not  obtain  good  results  with  calcium  treatment. 

Calcium  is  best  used  under  the  form  of  lactate.  Lactate  of  calcium  is 
given  by  mouth  or  rectum  in  a  10  per  cent,  solution,  4  grams  every 
three  hours,  or  subcutaneously  in  a  5  per  cent,  solution.  The  only 
inconvenience  connected  with  this  medication  is  that  it  must  be  given 
in  increasingly  large  doses.  Furthermore,  the  curt-  is  not  permanent 
but  lasts  only  as  long  as  the  medicament  is  used.  If  the  patient  still 
possesses  some  parathyroid  tissue,  calcium  lactate  may  tide  the  patient 
over  the  danger  period  until  the  parathyroid  tissue  has  undergone 
compensatory  hypertrophy. 

Hot  packs,  too,  are  a  good  therapeutic  measure  in  the  treatment  of 
tetany. 


532  POSTOPERATIVE  COMPLICATIONS 

Grafting  of  the  Parathyroids. — Two  different  conditions  may  occur. 

i.  During  operation  a  parathyroid  may  be  inadvertently  removed. 
In  that  case  there  must  be  no  hesitancy  as  to  what  should  be  done. 
This  parathyroid  must  be  reimplanted  at  once  in  the  thyroid  tissue 
which  is  to  be  left  in  situ,  as  shown  by  Halstead.  The  thyroid  is  selected 
on  account  of  its  rich  vascular  supply.  The  chances  for  success  for  this 
autotransplantation  are  very  good.  We  know  that  experimentally  it 
has  been  shown  time  and  time  again  that  autotransplantation  could  be 
made  successfully.  Christiani,  for  instance,  showed  that  transplanted 
parathyroids  could  be  still  physiologically  active  five  years  after  trans- 
plantation. 

2.  We  may  have  to  deal  with  a  patient  who,  during  operation  has 
been  deprived  of  one  or  more  parathyroids,  and  in  whom  a  marked  para- 
thyroid insufficiency  sometimes  occurs  later.  In  such  cases,  of  course, 
autotransplantation  is  out  of  the  question.  We  must  resort  to  hetero- 
transplantation. We  know  experimentally  that  in  the  majority  of  these 
cases  this  method  has  proved  to  be  a  failure.  Its  effects,  as  a  rule, 
are  only  temporary  and  last  only  during  the  time  necessary  for  the 
grafting  to  become  absorbed.  Consequently,  if  one  wishes  to  resort  to 
this  method  he  must  be  sure  that  there  exists  a  parental  relationship  as 
close  as  possible  between  the  donor  and  the  recipient.  The  ideal  would 
be  to  obtain  a  parathyroid  from  someone  closely  related  to  the  patient, 
as  father,  mother,  or  sister.  Not  only  such  close  parental  or  family 
relation  is  of  importance,  but  the  age,  sex  and  the  conditions  of  the  life 
of  the  donor  and  recipient  should  be  approximately  alike,  since  it  is 
easily  understood  why  a  parathyroid  removed  from  an  old  man  and 
transplanted  into  a  young  child  will  have  less  chance  to  be  successful 
than  if  the  donor  were  also  a  child.  If  all  these  requirements  are  met, 
the  grafting  may  then  become  permanent.  Such  an  operation  becomes, 
more  strictly  speaking,  a  homoiotrans plantation. 

In  order  to  be  successful  the  homoiotransplantation  must  take  place 
in  an  individual  in  whom  parathyroid  insufficiency  is  well  defined;  if 
that  is  not  the  case  the  grafting  will  not  "take."  This  fact  has  been 
demonstrated  experimentally  by  Halstead,  Christiani,  and  others.  On 
the  other  hand,  Iselin  has  shown  that  if  parathyroid  insufficiency  is  very 
marked,  the  chances  for  the  grafting  to  "take"  are  greatly  diminished. 
All  this  shows  that  the  conditions  of  nutrition  must  be  of  a  certain  kind 
to  allow  the  grafting  to  become  successful.  In  such  cases  it  is  better  to 
submit  the  individual  to  be  grafted  to  a  previous  treatment  with  lactate 
of  calcium  or  to  parathyroid  opotherapy. 

The  results  of  grafting  should  not  be  expected  to  become  noticeable 
before  six  to  ten  weeks. 

Have  we  the  right  to  parathyroidectomize  an  individual,  even  partially, 


PULMONARY  COMPLICATIONS  533 

in  order  to  benefit  another?  The  importance  of  the  parathyroids  is  too 
vital  to  deliberately  remove  one  or  two  parathyroids  from  one  patient 
in  order  to  benefit  another.  I  do  not  think  a  surgeon  should  do  so  even 
with  the  consent  of  the  donor,  for  who  knows  whether  the  parathyroid 
tissue  left  will  be  sufficient  to  meet  not  only  the  physiological  purposes, 
but  also  the  increased  demands  made  upon  the  system,  when  patholog- 
ical conditions  occur,  as  infectious  diseases,  etc.?  A  woman  who  is  liable 
to  become  pregnant  should  never  be  deprived  knowingly  of  one  or 
more  of  her  parathyroids,  because  eclampsia  seems  to  be  too  closely 
associated  with  parathyroid  insufficiency.  At  any  rate,  if  one  wants  to 
transplant  a  parathyroid  from  one  individual  to  another,  it  should  be 
done  only  after  having  ascertained  by  dissection  that  the  others  are 
seemingly  normal.  Everyone  who  has  had  some  experience  with  the 
dissecting  of  that  region  knows  how  difficult  it  is  sometimes  to  find 
the  parathyroids.  At  any  rate,  it  would  mean  a  long,  tedious  work 
which  might  endanger  the  life  of  the  very  organs  one  is  taking  so  much 
trouble  to  save.  Homoiotransplantation  should,  consequently,  not  be 
undertaken  unless  for  some  especially  strong  motives. 

The  only  possibility  which  then  remains  is  to  take,  as  Kocher  did, 
the  parathyroids  from  someone  who  has  just  died  bv  suicide,  or  as 
Pool  did,  from  someone  who  had  died  from  a  disease  which  would  not 
prove  to  be  detrimental  to  the  recipient.  The  shortest  possible  time 
should  be  allowed  to  elapse  between  the  removal  and  the  transplanta- 
tion. The  best  thing  to  do  is  to  dissect  the  parathyroids  as  soon  as 
possible  after  death  of  the  donor  and  to  put  them  in  a  warm  Locke 
solution,  or  better,  in  the  blood  serum  of  the  recipient  himself  while  he 
is  being  prepared.  The  method  known  as  the  method  en  semis,  spoken 
of  when  dealing  with  transplantation  of  the  thyroid,  may  be  used  here, 
especially  if  the  parathyroids  are  of  good  size.  One  or  more  parathy- 
roids may  be  used. 

The  place  of  choice  for  parathyroid  transplantation  is  the  same  as 
for  thyroid  transplantation.  It  may  be  done  either  in  the  abdominal 
walls  between  the  muscles  and  the  peritoneum  or  in  the  tibia.  The 
thyroid  itself  and  the  spleen  should  afford  good  chances  for  success. 
The  same  rules  indicated  for  thyroid  grafting  apply  for  parathyroid 
transplantation.  I  he-  operation  should  be  done  very  rapidly;  the  gland- 
ule should  be  handled  with  greatest  care  and  gentleness;  hemostasis  of  the 
cavity  where  the  grafting  is  done  should  be  absolutely  perfect,  and  no 
antiseptic  whatsoever  should  be  used  for  the  instruments,  the  hands,  etc. 

Pulmonary  Complications.  For  a  long  time  pneumonia  and  broncho- 
pneumonia had  been  among  the  postoperative  complications  threat- 
ening most  the  life  of  the  goiter  patient.  I  Ins  was  due  partly  to  the 
fact  that  at  that  time  large  goiters  with  their  complications  were  fre- 


534  POSTOPERATIVE  COMPLICATIONS 

quently  seen  and  partly  to  the  indiscriminate  and  ignorant  use  of  the 
anesthetic.  Nowadays  the  operations  are  done  to  patients  whose  gen- 
eral condition  is  better.  We  understand  the  use  of  the  anesthetics 
better,  and  we  are  more  skilful  in  administering  them.  Consequently 
pneumonia  and  bronchopneumonia  are  certainly  much  rarer  complica- 
tions than  formerly.  In  all  my  cases  I  have  had  only  once  a  case  of 
pneumonia,  and  that  was  following  tracheotomy. 

Postoperative  Dysphagia. — After  operation  for  simple  or  toxic  goiter 
the  patients  often  complain  of  dysphagia  for  twenty-four  to  forty-eight 
hours.  This  is  likely  due  to  the  involvement  of  the  esophagus  in  the 
aseptic  inflammatory  processes  following  the  operation,  and  possibly 
to  the  injury  of  some  of  the  pharyngo-esophageal  plexus,  during  the 
various  manipulations  occasioned  by  the  removal  of  the  goiter. 

Postoperative  Hematoma. — Despite  the  greatest  care  in  ligating 
every  bleeding  vessel,  and  especially  when  no  drainage  has  been  used, 
postoperative  hematoma  is  sometimes  observed.  It  is  an  unpleasant 
but  insignificant  complication.  This  postoperative  hematoma  is  better 
left  alone.  It  often  drains  spontaneously  ten  to  fifteen  days  after.  If 
not,  and  if  at  that  time  the  swelling  is  still  marked,  some  of  the  blood 
may  be  aspirated  with  an  aspirative  syringe,  cautiously  in  order  to  avoid 
a  fresh  hemorrhage  a  vacuo. 

Raising  of  the  Scar. — In  spite  of  the  greatest  care  on  the  part  of  the 
surgeon,  some  patients  will  sometimes  "raise"  a  scar  and  form  large, 
thick,  unsightly  elevations  resembling  cheloids.  In  some  cases  the  sur- 
geon is  really  not  to  blame  for  this  since  it  is  a  pathological  peculiarity 
ot  the  patient.  In  the  majority  of  cases  the  raising  of  the  scar,  however, 
is  due  to  a  "bevelled"  incision.  Hence  the  necessity  for  using  a  fine, 
sharp  knife  and  of  holding  it  perpendicular  to  the  skin  while  cutting. 

After-treatment. — I  cannot  do  better  than  to  quote  the  entire 
section  of  Ochsner's  paper  bearing  on  this  subject: 

"By  far  the  most  important  point  in  the  surgical  consideration  of 
this  condition  consists  in  the  after-treatment,  because  with  careful 
after-treatment  almost  all  of  these  patients  may  become  nearly  as  use- 
ful as  they  were  before  they  began  to  suffer  from  exophthalmic  goiter, 
while  in  cases  in  which  the  after-treatment  is  not  carefully  carried  out, 
practically  all  of  these  patients  develop  a  condition  as  bad,  if  not  worse, 
than  that  with  which  they  presented  themselves  primarily  for  surgical 
treatment.  The  surgeon  should  bear  in  mind,  in  the  first  place,  that 
practically  all  of  these  patients  belong  to  a  class  of  neurotics,  and  that 
this  undoubtedly  had  much  to  do  with  the  development  of  their  goiters 
primarily,  and  that  unless  this  condition  is  carefully  taken  into  consid- 
eration in  the  after-treatment,  the  weakened  physical  condition  of  the 
patient  will  not  be  able  to  bear  the  wear  and  tear  to  which  the  neurotic 


RULES  FOR  GOITER  PATIEXTS  535 

tendencies  would  surely  expose  the  patient.  The  same  is  true  concern- 
ing the  diet  which  is  habitually  chosen  by  the  patients,  which  is  usually 
exceedingly  unwholesome,  and  it  is  consequently  important  that  they 
be  impressed  with  the  fact  that  unless  they  will  adhere  to  the  use  of  a 
reasonable  diet,  their  chances  for  permanent  recover)'  will  be  very 
slight.  We  have  always  given  these  patients  printed  directions  which 
contain  all  of  the  important  rules  to  be  observed,  and  we  have  advised 
the  patients  to  read  these  directions  at  regular  intervals  and  to  follow 
them  for  many  years.  The  following  is  a  copy  of  the  directions  which 
we  use  in  these  cases,  and  which  have  proved  eminently  satisfactory. 
The  patient  received  a  mild  tonic  and  a  laxative  and  an  absolute  diet 
list  upon  leaving  the  hospital. 

Rules  for  Goiter  Patients. —  I.  You  should  avoid  all  excitement 
or  irritation,  like  attending  receptions,  shopping,  church  work,  and 
politics. 

2.  You  should  get  an  abundance  of  rest  by  going  to  bed  early,  and 
taking  a  nap  after  luncheon. 

3.  You  should  have  an  abundance  of  fresh  air  at  night,  consequent!)' 
you  should  sleep  with  wide-open  windows  or  on  a  sleeping  porch. 

4.  You  should  eat  and  drink  nothing  that  irritates  the  nervous  sys- 
tem, like  tea,  coffee,  or  alcohol.  Of  course  you  should  not  use  tobacco 
in  any  way. 

5.  You  should  eat  very  little  meat.  If  you  are  fond  of  meat,  take 
a  little  beef,  mutton,  or  breast  of  chicken,  or  fresh  fish  once  or  twice  a 
week,  or  at  most,  three  times  a  week. 

6.  You  should  drink  a  great  deal  of  milk  or  eat  things  that  are  pre- 
pared with  milk,  such  as  milk  soup,  milk  toast,  etc.;  cream  and  buttermilk 
are  also  especially  good  for  you. 

7.  You  should  avoid  beef  soup  or  beef  tea  or  any  kind  of  meat  broths. 

8.  You  should  eat  an  abundance  of  cooked  fruits  and  cooked  vege- 
tables or  very  ripe  raw  fruits,  or  drink  fruit  juices  prepared  out  ol  ripe 
fruits. 

9.  You  may  eat  eggs,  bread  and  butter,  toa^t,  rice,  cereals. 

10.  You  should  drink  an  abundance  of  good  drinking-water,  or  if  this 
is  not  available,  you  should  boil  your  drinking-water  for  a  few  minutes 
or  drink  distilled  water." 


CHAPTER   LI. 

THE  THYMUS   GLAND. 

'  Synonyms. — English,  sweetbread;  French,  riz-de-veau;  German, 
Briesel,  Brosel,  Kalbsmilch,  Lactes. 

History  and  Etymology. — The  first  mention  of  the  thymus  gland  in 
the  literature  was  made  by  Polydeukes  and  Rufus,  while  Vasal  and 
Bartholinus  were  the  first  to  give  descriptions  and  pictures  of  it.  For 
some  authors  the  word  "thymus"  comes  from  the  Greek  word  dvfxos 
which  means  "the  thyme"  and  was  used  to  designate  the  gland  on 
account  of  some  resemblance  in  the  shape  of  the  thymus  gland  and 
the  leaves  of  that  plant.  For  Galen  the  word,  "thymus"  comes  from 
the  Greek  dvfxds  which  means  "courage"  and  was  applied  to  the  thymus 
on  account  of  the  intimate  relation  of  that  gland  with  the  heart. 

Embryology. — The  thymus  gland  is  present  in  all  the  vertebrates;  it 
has  not  yet  been  found  in  the  Amphyoxus.  Developed  from  the  third 
branchial  cleft,  the  thymus  lies  at  first  in  very  close  contact  with  the 
thyroid  and  the  parathyroids.  Later  on,  however,  in  embryonic  life 
the  thymus  passing  in  front  of,  very  seldom  behind,  the  left  innominate 
vein,  descends  into  the  superior  mediastinal  space  and  spreads  over  the 
pericardium,  thus  becoming  entirely  intrathoracic.  GrosschufF,  in  1896, 
showed  that  the  thymus  did  not  take  its  origin  from  the  third  branchial 
cleft  alone,  but  that  in  a  great  number  of  animals  such  as  the  dog,  goat, 
sheep,  etc.,  the  thymus  is  developed  from  the  fourth  branchial  cleft 
also.  This  close  relation  of  the  thymus  with  the  thyroid  and  the  para- 
thyroids will  explain  the  origin  of  the  thymic  nodules  which  are  found, 
not  only  around  the  lateral  regions  of  the  thyroid,  but  also  in  the  midst 
of  the  parenchyma  itself.  These  intrathyroid  nodules,  according 
to  Grosser  and  Betke,  are  more  or  less  constant  in  young  children 
up  to  two  or  three  years  of  age.  They  are  frequently  found  in  specimens 
of  later  life,  provided,  one  searching  for  them  takes  the  time  to  make 
seriated  slides.  The  knowledge  of  the  existence  of  such  accessory 
thymic  nodules  is  important  since  it  has  been  shown  experimentally 
that  after  complete  thyroidectomy  these  nodules  undergo  a  compen- 
satory hypertrophy.  They  may  also  play  a  part  in  the  production 
of  hyperthyroidism;  finally,  they  may  give  rise  to  the  development  of 
tumors. 

In  early  embryonic  life  each  lobe  of  the  thymus  has  an  excretory 
canal  connecting  the  gland  with  the  third  branchial  cleft.     This  is  called 


PLATE    XXVII 


Jibuti*? 


Thymus  of  Newborn   Baby  (Natural  Size). 

Note  that  the  thymus  fills  almost  the  entire  mediastinum  and  extends  upward  as  far 
as  the  thyroid  gland.  1  he  figure  illustrates  very  well  what  is  called  the  "cervical"  and 
the  "intrathoracic"  portions  of  the  thymus.  Note,  too,  the  vessels  extending  from  the 
thyroid   to   the   thvmus. 


SURGICAL  AX  ATOMY  OF  THE  THYMUS  537 

the  thymopharyngeal  duct.  This  canal,  however,  undergoes  atrophy  in 
the  beginning  of  the  third  month  of  embryonic  life.  Like  the  thyro- 
glossus  duct,  the  thymopharyngeal  duct  sometimes  remains  patent, 
thus  causing  the  production  of  cervical  fistulae  whose  feature  it  is  to 
be  always  lateral,  while  the  fistulae  developed  from  the  thyroglossus  duct 
are  always  median.  Thymopharyngeal  fistulae  begin  on  the  lateral  wall 
of  the  pharynx  a  little  below  the  fossa  tonsillaris;  extend  downward, 
passing  above  and  m  front  of  the  hypoglossus  nerve,  then  run  between 
the  carotids  and  reach  the  inner  border  of  the  sternocleidomastoid 
muscle,  which  they  follow  until  they  break  through  the  skin,  usually  a 
little  above  the  clavicle.  In  other  instances  the  thymopharyngeal  duct 
becomes  obliterated  partially,  so  that  only  portions  of  it  remain.  These 
portions  are  then  liable  to  give  rise  to  cystic  or  solid  tumors.  The 
thymopharyngeal  canal,  like  the  thyroglossus  duct,  is  lined  with  ciliated 
epithelium,  which  in  some  instances,  however,  may  be  low  or  cuboidal. 

Histology. — Histologically,  the  thymus  is  composed  of  two  portions, 
the  cortical  and  the  medullary.  The  medullary  portion  is  composed  of 
a  meshwork  of  giant  and  syncytial-hke  cells  and  of  Hassal's  corpuscles; 
lymphocytes  are  found  here  only  in  moderate  numbers.  On  the  other 
hand,  the  cortical  portion  is  composed  of  basophile  lymphocytes  and 
eosinophiles  mostly.  The  eosinophiles  are  very  abundant  from  the 
seventh  month  of  embryonic  life  up  to  a  few  months  after  birth;  they 
then  diminish  very  rapidly  in  number  during  the  first  years  of  life  and 
are  mostly  absent  after  the  tenth  or  twelfth  year.  No  one  is  yet  clear 
as  to  the  origin  and  real  significance  of  Hassal's  corpuscles.  By  some 
they  are  regarded  as  of  epithelial  origin,  while  by  others  they  are  con- 
sidered as  the  remainder  of  the  thymic  ducts.  The  thymus  must  be 
regarded  as  a  lympho-epithelial  organ. 

Surgical  Anatomy  of  the  Thymus. — The  thymus  is  formed  by  two 
lobes  which  are  in  close  relation,  one  with  the  other,  but  entirely  inde- 
pendent; no  isthmus  is  present. 

The  thymus  lies  in  the  upper  and  anterior  portion  of  the  mediastinal 
space,  just  behind  the  manubrium  and  corpus  sterni.  It  covers  the 
basis  of  the  heart,  the  origin  of  the  thoracic  vessels  such  as  the  aorta, 
pulmonary  artery,  the  innominate  veins  and  arteries,  and  the  vena  cava 
and  the  trachea  (Plates  XXVII  and  XXVIII).  Furthermore,  the 
thymus  comes  in  contact  with  the  vagus,  inferior  laryngeal  and  phrenic 
nerves;  laterally,  it  comes  in  contact  with  the  pleural  membrane.  In 
cases  of  extreme  hyperplasia,  the  thymus  covers  the  entire  pericardium 
and  may  reach  the  diaphragm.  In  children  the  upper  pole  oi  the  thymus 
extends,  as  a  rule,  i  or  2  cms.  above  the  episternal  notch.  Sometimes 
these  poles  come  in  contact  with  the  lower  poles  oi  the  thyroid.  In 
adults  the  thymus  when  hypertrophied  does  nor,  as  a  rule,  extend  very 


538 


THE  THYMUS  GLAND 


far  above  the  episternal  notch.  Between  the  upper  poles  of  the  thymus 
and  the  lower  poles  of  the  thyroid  a  connective-tissue  ligament  contain- 
ing thymic  vessels  coming  from  the  inferior  thyroid  artery  is  more  or 


Fig.  90. — A,  thyroid;   B,  lungs;   C,  thymus;  D,  heart. 

less   always   present;   this  ligament  is   called   the    thyrothymic  ligament. 
(Plates  XXVII,  XXVIII  and  Fig.  90.) 

The  blood  supply  of  the  thymus  comes  from  the  inferior  thyroid  and 
the  internal  mammary  arteries;    sometimes  direct  branches  are  given 


INVOLUTION  OF  THE  THYMUS 


539 


off  from  the  subclavian  artery.  From  below  it  receives  blood  from  a 
pericardiophrenic  branch.  (Plate  XXVIII.)  Its  lymphatics  run  into 
the  intrathoracic  lymph  nodes.  The  nerve  supply  comes  from  the 
sympathetic,  the  vagus,  and  according  to  Marfan,  from  the  phrenic. 

Involution  of  the  Thymus. — It  was  formerly  thought  that  the  thymus 
after  birth  grew  up  to  the  second  year,  then  gradually  diminished  and 
disappeared  more  or  less  entirely  after  the  thirtieth  year  of  life.  Today 
it  is  more  generally  understood  that  the  thymus  is  an  organ  belonging 
to  the  period  of  development.  As  soon  as  the  physical  development  has 
reached  its  completion,  the  organism  seems  to  have  no  more  need  of 
that  organ,  hence  its  atrophy.  Consequently  it  must  be  expected  that  we 
find  this  gland  increasing  in  size  and  weight  during  the  period  of  growth, 
and  so  it  is.  According  to  Hammar  this  gland  reaches  its  maximum  of 
size  between  the  eleventh  and  fifteenth  years,  its  normal  weight  being 
about  37  grams.  It  then  diminishes  gradually  until  vestiges  only  are 
found  in  later  life.  The  first  to  disappear  are  the  cortical  and  next  the 
medullary  portions;  in  the  final  stage  of  involution  Hassal's  corpuscles 
onlv  are  found  as  the  last  vestiges.  This  is  known  as  the  physiological 
involution. 

The  following  table  of  weights  of  the  thymus  at  varying  ages  is 
given  by  Hammar: 

Newborn     . 

I  to    5  years 

6  to  io  years 
II  to  15  years 
16  to  20  years 
21  to  25  years 
26  to  35  years 
36  to  45  years 
46  to  55  years 
56  to  65  years 
66  to  75  years 


13.26 

grams 

22.98 

it 

26.  IO 

tt 

37-52 

a 

25-58 

u 

24-75 

k 

19.87 

it 

16.27 

<< 

12.85 

a 

16.08 

a 

6.00 

M 

It  is  an  interesting  fact  that  the  thymus  of  animals  undergoes  a  very 
marked  involution  when  the  animals  are  starved  for  a  certain  period 
of  time,  and  that  both  the  cortical  and  medullary  portions  of  the  thy- 
mus undergo  atrophy,  while  the  connective  tissue  increases.  At  the 
same  time  fatty  degeneration  invades  the  gland.  This  is  known  as  the 
pathological  involution.  The  same  involution  takes  place  in  pathological 
conditions  especially  in  acute  diseases  such  as  pneumonia,  nephritis,  etc. 
Usually,  the  involution  is  a  temporary  one  and  when  the  acute  process 
is  over,  the  organ  returns  to  its  previous  normal  condition.  In  diseases 
of  standing,  however,  this  is  no  longer  true;  there  the  thymus  under- 
goes a  sclerosis  which  remains  permanent.    Involution  is  then  permanent. 


540  THE  THYMUS  GLAND 

Experimental  Pathology  of  the  Thymus. — After  total  thymectomy 
there  is  at  first  no  change  in  the  external  habitus  of  the  animal.  Three 
or  four  weeks  later,  however,  the  animal  begins  to  show  retarded  growth 
and  diminution  of  weight  and  acquires  a  spongy,  pasty  appearance  due 
to  fatty  degeneration.  Here  we  have  the  stage  of  increased  adipose 
tissue.  Cachexia,  however,  soon  follows  that  stage.  The  hair  falls 
out;  extreme  muscular  weakness  takes  place,  and  a  marked  tremor 
becomes  apparent.  The  animal  becomes  apathetic  and  gradually  enters 
into  a  state  of  idiocy  similar  to  the  one  seen  in  thyroid  insufficiency. 
This  cachectic  stage  may  last  from  three  to  twenty  months,  and  then 
death  takes  place  after  the  animal  has  been  in  a  state  of  thymic  coma 
with  absolute  loss  of  consciousness  lasting  several  days.  In  cases  where 
the  removal  of  the  thymus  has  not  been  complete,  regeneration  of  the 
gland  may  take  place,  and  a  gradual  restoration  to  health  may  follow. 

Skeleton. — Complete  thymectomy  performed  in  very  young  animals 
has  a  marked  effect  upon  the  after-development  of  the  osseous  system, 
as  was  shown  by  Klose,  Matti,  and  others.  The  bones  become  soft  and 
rachitic,  showing  curvatures  and  deformities.  This  osteomalacia,  involv- 
ing especially  the  spinal  column,  affects  also  the  pelvic  bones,  thorax 
and  skull.  From  an  histological  point  of  view  one  will  see  that  the 
epiphyseal  line  is  abnormally  enlarged  and  very  irregular;  that  the  bones 
show  a  deficiency  of  calcareous  compounds  in  the  cortical  portion,  and 
that,  instead  of  65  per  cent,  of  calcium  salts  which  bones  normally  con- 
tain, they  have  only  32  to  34  per  cent,  of  these  salts,  while  the  trabeculae 
of  the  spongiosa  are  thinner  and  fewer.  The  changes  occurring  in  the 
skeleton  following  thymectomy  must  be  regarded  as  similar  to  those 
found  in  rickets,  and  are  caused  by  a  deficiency  of  calcareous  material 
in  the  osseous  system.  If  this  insufficiency  occurs  in  a  growing  skeleton, 
rickets  with  all  its  deformities  will  follow,  but  if  this  insufficiency  occurs 
in  an  already  fully  developed  bone,  osteomalacia  and  osteoporosis  only 
will  be  the  results. 

Nervous  System. — In  thymectomized  animals  H.  Vogt  found  swell- 
ing of  the  brain,  of  the  ganglia  and  the  glia  cells,  and  he  found,  too,  an 
increased  amount  of  gray  matter.  The  ganglia  and  the  glia  cells  are 
not  only  swollen,  but  are  also  degenerated.  This  swelling  of  the  nervous 
elements  is  due  to  an  increased  retention  of  water  among  the  elements, 
most  likely  due  to  an  increased  acidity  of  the  blood  serum.  This  acid- 
osis may  be  caused  by  an  actual  increase  of  the  acid  contents  of  the  blood, 
or  may  be  due  possibly  to  the  absence  of  substances  destined  to  counter- 
balance the  acidity.  This  fact,  too,  is  exceedingly  interesting  and  of 
practical  importance,  because  as  we  know,  acidosis  frequently  follows 
an  operation  for  exophthalmic  goiter  and  is  always  a  dreaded  compli- 
cation, since  it  often  terminates  in  coma  and  death. 


PLATE    XXVIII 


TAuroid 

fnternal 'jugular  ¥■- 
Common  carotid 

Thuro-ffiym'C  /lynmen, 
unfhifc  "arc.  branches 


In  nominate  Vein 


TAymus 
Phrenic  Jferve 
Subclavian  Srartcn 


Normal  Anatomical   Relations  of  the    Thymus   to  the 
Other  Organs. 


Newborn   Baby    Having 
"Thymic  Death.' 

Note  the  enormous   size  of  the 
pared  with   the  size  of  the  heart, 
intimate  relation  between  the  thymi 
through  the  thyrothvmic  ligament. 


EjOtolnq 


INTERRELATION  OF   THYMUS  TO  ORGANS  OF  SECRETION       541 

Muscular  System. — After  a  certain  period  of  time  thymectomized 
animals  show  an  extreme  muscular  weakness  and  tremor.  The  muscles 
have  lost  their  striation;  their  sarcolemma  and  external  perimysium 
have  become  thickened  and  swollen;  the  muscular  fibers  are  atrophied; 
the  connective  tissue  is  very  much  increased  and  swollen;  the  actual 
content  of  the  musculature  is  manifestly  decreased. 

At  first  these  findings  seem  to  throw  some  light  toward  a  satisfactory 
explanation  of  the  muscular  symptoms  seen  in  Basedow's  disease. 
Indeed,  the  muscular  asthenia  seen  in  such  cases  is  exceedingly  marked. 
It  would  therefore  seem  that  most  of  these  muscular  symptoms  seen  in 
thyrotoxicosis  are  due  to  thymus  insufficiency,  yet  it  is  a  well-known 
fact  that  in  Basedow's  disease  the  thymus,  instead  of  being  atrophied, 
is  hyperplastic.  On  the  other  hand,  we  know  that  myasthenia  gravis 
is  often  accompanied  by  thymus  hyperplasia.  The  musculature  in  such 
cases  shows  marked  pathological  changes  such  as  round-cell  infiltration, 
fatty  degeneration,  etc.  Whatever  the  final  explanation  may  be,  we 
must  admit,  nevertheless,  that  there  is  some  relation  between  the  thymus 
and  the  muscular  system. 

Interrelation  of  the  Thymus  to  the  Organs  of  Internal  Secretion. — As 
shown  by  such  authors  as  Basch,  Matti,  and  Klose,  there  is  an 
intimate  relation  between  the  thymus  and  the  thyroid.  After  thymec- 
tomy the  thyroids  of  animals  used  for  experimentation  become  mani- 
festly hyperplastic;  the  follicles  become  larger,  the  epithelium  higher, 
having  the  tendency  to  become  cylindrical;  in  short,  the  thyroid  gland 
shows  in  a  general  way  the  histological  picture  of  the  thyroid  gland  seen 
in  Basedow's  disease.  The  reverse  is  true,  too,  namely,  that  after  thy- 
roidectomy the  thymus  undergoes  hyperplasia.  This  fact  is  also  of  great 
practical  importance  since  it  will  allow  us  to  understand  why  after  an 
operation  for  goiter  we  may  have  to  deal  with  mechanical  as  well  as 
functional  disturbances  due  to  an  increased  thymic  hyperplasia. 

In  12  cases  of  mors  thymica  in  newborn,  Hedinger  found  7  cases 
with  enlargment  of  the  thyroid  gland.  In  goiterous  regions,  especially 
in  Bernese  regions  where  goiter  is  endemic,  the  thymus  hypertrophy 
and  struma  in  newborn  is  exceedingly  frequent.  In  1910,  in  the  Bernese 
Pathological  Institute,  44  postmortems  of  newborn  were  made.  In 
12  of  these  cases  the  thymus  hyperplasia  was  extremely  marked  and 
the  goiters  were  of  large  size.  In  several  cases  the  hyperplasia  of  the 
goiter  and  thymus,  although  quite  marked,  was  not  as  pronounced  as 
in  the  cases  just  mentioned,  and  only  in  3  cases  were  there  concomitant 
goiters.  In  adults  this  combination  of  thymus  hyperplasia  and  goiter 
is  extremely  frequent,  as  has  been  reported  by  Virchow,  Gluck,  Wiens, 
Weber,  Nettel,  Kaufmann,  Rossle,  Hair,  and  myself. 


542  THE  THYMUS  GLAND 

The  parathyroids,  too,  undergo  a  marked  hyperplasia  after 
thymectomy. 

It  is  a  very  interesting  fact,  too,  that  after  thymectomy  the  supra- 
renal bodies  undergo  marked  hyperplasia  whereas,  in  cases  of  thymic 
hyperplasia  the  chromaffin  system  seems  to  be  decidedly  diminished, 
hence  the  conclusion  that  there  is  possibly  an  antagonism  between  these 
two  systems.  The  same  is  true  for  the  genital  system,  so  that  there 
seems  to  be  a  decided  antagonism  between  these  two  apparatuses. 
After  complete  thymectomy  the  testicles  become  manifestly  hyper- 
plastic. It  has  been  generally  observed  that  in  cases  of  status  thymo- 
lymphaticus the  development  of  the  genital  apparatus  is  very  much 
retarded,  while,  on  the  other  hand,  it  seems  that  in  young  individuals 
whose  genital  system  is  prematurely  developed,  the  involution  of  the 
thymus  occurs  at  an  earlier  period.  This  is  another  point  in  favor  of 
considering  the  genital  apparatus  and  the  thymus  as  two  antagonistic 
systems. 

Status  Thymolymphaticus. — Thymus  hyperplasia  is  not  infrequently 
combined  with  a  concomitant  hyperplasia  of  the  entire  lymphatic  sys- 
tem. The  tonsils  and  adenoids  are  enlarged;  the  lymphatic  ganglions 
and  their  follicles  are  hyperplastic;  the  follicles  of  the  basis  of  the  tongue 
are  markedly  increased;  the  spleen  is  larger  than  normally;  the  adenoid 
tissue  of  the  entire  lymphatic  apparatus  is  involved.  This  condition  is 
known  as  the  status  lymphaticus  of  Paltauf.  When  there  is  a  concomi- 
tant hyperplasia  of  the  thymus  the  condition  is  then  known  as  status 
thymolymphaticus .  This  condition  is  accompanied  by  a  reduced  caliber 
of  the  aorta  and  of  the  arterial  system.  The  patients  affected  with 
status  thymolymphaticus  are  pale,  yellowish  in  color,  although  more  or 
less  well  nourished.  It  is  often  said  of  them  that  they  have  a  lymphatic 
habit,  a  condition  which  is  more  easily  recognized  than  described.  Such 
patients  have  a  diminished  resistance;  they  are  more  vulnerable  to  and 
stand  a  good  deal  less  than  others,  bacterial  and  toxic  influences.  Their 
nervous  system  is  impaired;  their  cardiac  function,  for  some  reason  or 
other,  is  easily  inhibited  and  death  from  cardiac  paralysis  in  such  cases 
is  frequent. 

Thymic  Tracheostenosis. — The  most  striking  symptom  of  thymic 
hyperplasia  is  dyspnea.  This  may  be  characterized  by  a  labored  respira- 
tion only,  or  by  the  most  intense  choking  spell.  Between  these  two 
extremes  all  forms  of  transition  are  found.  Dyspnea  may  be  constant 
or  intermittent,  and  with  or  without  acute  paroxysms.  Between  attacks 
respiration  may  be  normal.  There  may  be  a  constant  and  persistent 
inspiratory  stridor,  and  in  extreme  dyspnea,  an  expiratory  stridor  may 
also  be  found,  which,  however,  is  less  marked.  The  choking  spell  may 
occur  without  cause,  or  when  the  child  cries  from  pain  or  anger.     Hyper- 


PLATE   XXX 


The  relation  of  the  innominate  of  the  common  carotid  and  aorta 
to  the  vagus  and  inferior  laryngeal  nerves.  It  will  be  easily  seen 
how  a  tumor  compressing  and  displacing  these  large  vessels  will 
put  the  inferior  laryngeal  nerve  on  the  stretch,  thus  causing  closure 
of  the  glottis  and  choking  spell.  The  figure  shows,  too,  where 
compression  on  the  windpipe  by  the  thymus  will  take  place. 


PLATE    XXXI 


Thymectomy. 

The  two  flaps  obtained  after  the  transverse  incision  has  been  made  are  retracted  and  the 
superficial  cervical  fascia  is  grasped  between  two  forceps  and  cut  in  the  middle  line. 


Thymectomy. 
The  prethyroid  muscles  are  divided  in  the  middle  line  and  retracted  laterally. 


CHROXIC  FORM  OF   THYMIC  HYPERPLASIA  543 

extension  of  the  head  or  dorsal  decubitus  exaggerates  dyspnea.  This 
would  explain  why  dyspnea  is  more  marked  during  sleep  than  during 
waking  hours.  The  choking  spells  may  last  but  a  few  minutes,  or  a 
few  hours,  or  a  few  days,  and  then  respiration  becomes  normal  again. 
In  other  cases  death  ensues.  In  certain  cases  the  child  dies  at  the 
beginning  of  the  choking  spell. 

This  dyspneic  condition  begins,  as  a  rule,  in  the  first  weeks  or 
months,  diminishes  during  the  second  year  of  life  and  is  seldom  found 
after  this  period.  This  may  be  due  to  the  fact  that  the  gland  normally 
retrocedes  after  the  second  year  of  life  and  that  the  superior  opening  of 
the  thorax  becomes  larger  with  the  growth  of  the  child. 

In  children  the  dyspneic  symptoms  due  to  thymic  hyperplasia  may 
be  acute  or  chronic. 

Acute  Symptoms. — Certain  cases  of  asphyxia  of  newborn  babies  can  be 
explained  only  by  thymic  hyperplasia.  In  such  cases  the  child  is  born 
apparently  dead,  so  that  it  often  takes  quite  a  long  time  to  bring  it 
back  to  life.  Cyanosis  is  marked,  breathing  remains  difficult  and  loud; 
in  many  instances  the  child  dies  after  a  few  minutes  or  hours.  Post- 
mortem examination  shows  compression  of  the  windpipe  by  a  hyper- 
plastic thymus  (Plate  XXIX).  In  other  instances  the  child  may 
have  been  in  good  health  for  weeks  or  months  when  a  most 
unexpected  choking  spell  comes  up.  Suddenly,  without  any  apparent 
cause,  or  possibly  after  a  few  spells  of  moderate  dyspnea  to 
which  little  attention  has  been  paid,  the  child  throws  his  head 
backward  and  makes  intense  efforts  to  get  his  breath.  He  rolls 
his  eyes  upward  and  his  face,  especially  the  lips  and  tongue, 
become  cyanotic  and  swollen.  The  veins  of  the  neck  are  congested,  and 
a  loud  stridor  is  present.  The  entire  accessory  respiratory  musculature 
is  called  into  play.  A  marked  "tirage"  of  the  supra-  and  of  the  infra- 
sternal  fossae  is  noticed.  Soon,  however,  everything  relaxes  and  the 
pupils  become  widely  dilated;  cyanosis  subsides  and  is  soon  replaced  by 
a  gray,  ash-like  color;  the  lips  and  tongue  become  livid.  The  child  is 
dead.  No  one  has  had  time  fully  to  realize  what  was  going  on.  We 
have  all  lived  through  such  cases  and  have  all  remained  stunned  and 
speechless  at  the  sudden  and  unexpected  outcome  of  the  drama. 

Chronic  Form  of  Thymic  Hyperplasia. — Fortunately,  all  cases  do  not 
have  such  a  fulminating  character.  The  choking  spells  are  not  all 
fatal;  they  subside  soon  and  are  replaced  by  intervals  of  quiet  and  easy 
breathing.  Often,  however,  the  respiration  remains  labored  all  the  way 
through  the  attack.  These  cases  are  the  ones  in  which  an  early  recog- 
nition of  the  condition  and  prompt  surgical  treatment  will  save  the 
patient's  life. 

In  children  what  might  be  termed  a  latent  thymus  hyperplasia  may 


544 


THE  THYMUS  GLAND 


exist  for  a  longer  or  a  shorter  period  of  time.  Such  cases,  as  a  rule,  do 
not  come  under  surgical  jurisdiction.  They  are  seen  by  the  family 
physician  who  finds  that  the  child  is  in  poor  general  condition  and 
suffering  from   some  vague   respiratory   disturbances.      The   physician 


Fig.  91. — Showing  how  the  thymus  during  hyperextension  of  the  head  or 
coughing  comes  up  like  a  wedge  and  is  caught  at  the  superior  opening  of  the  thorax,  thus 
compressing  the  trachea. 


may  or  may  not  connect  these  symptoms  with  thymus  hyperplasia; 
but  even  if  he  makes  a  correct  diagnosis  the  parents  will  likely  never 
consider  an  operation  necessary  until  more  decided  dyspneic  symptoms 
are  present.  But  unfortunately,  sudden  death  is  sometimes  the  first 
symptom  which  reveals  the  latent  form  of  thymus  hyperplasia,  and  in 


PRESSURE  AT  SUPERIOR  OPEXIXG  OF  THORAX  545 

a  great  many  cases  this  unsuspected  condition  is  revealed  only  at  the 
autopsv.  Today,  however,  since  we  know  a  little  more  of  this  patholog- 
ical condition,  I  believe  that  this  fulminating  form  of  death  without  any 
prodromic  symptoms  is  rare.  As  a  rule  the  learned  physician  will  find 
in  the  history  of  these  cases  a  few  symptoms  which,  if  well  interpreted, 
will  arouse  the  suspicion,  at  least,  of  a  hyperplastic  thymus.  As 
in  Blight's  disease,  so  there  are  in  thymus  hyperplasia,  too,  some 
minor  symptoms  which  will  lead  the  physician  to  a  correct  diag- 
nosis. But  it  is  just  because  such  symptoms  have  not  been  carefully 
observed  that  the  diagnosis  of  thymic  hyperplasia  is  not  made;  as  a 
result  the  child  is  found  dead  in  his  bed;  autopsy  shows  a  large  thymus 
compressing  the  windpipe. 

Explanation  of  the  Choking  Spells  and  of  Thymic  Death. — How  are 
we  to  explain  the  pathogen)'  of  these  choking  spells  ?  Pressure  may 
take  place  at  two  points: 

i.  At  the  superior  opening  of  the  thorax. 
2.   In  the  thorax. 

Pressure  at  the  Superior  Opening  of  the  Thorax. — We  know  that  in 
young  infants  the  anteroposterior  diameter  of  the  superior  opening  of 
the  thorax  is  quite  small  and  that  it  does  not  exceed  2  or  3  centi- 
meters. Because  of  the  relation  of  the  thymus  with  the  thyroid,  with 
which  it  is  connected  by  the  thyrothymic  ligament,  the  thymus  will 
follow  the  up-and-down  movements  of  the  windpipe  and  larynx,  during 
the  various  acts  of  swallowing,  coughing,  and  hyperextension  of  the 
head,  etc.  A  finger  placed  behind  the  episternal  notch  feels  the  impact 
of  the  rising  thymus.  Consequently  the  thymus  when  hyperplastic 
comes  up  like  a  wedge  between  the  spinal  column  and  the  manubrium 
sterni  CFig.  91).  There  it  is  caught  and  constricted  at  the  superior 
opening  of  the  thorax,  the  so-called  "critical  space."  Inasmuch  as  the 
bony  ring  which  forms  the  superior  opening  of  the  thorax  is  non-elastic, 
the  organs  which  it  contains  must  necessarily  undergo  compression. 
Since  the  trachea  lies  immediately  below  the  thymus  it  is  the  first  to  be 
compressed,  hence  the  choking  spells  (  Fig.  91  ). 

If  the  superior  opening  of  the  thorax  cannot  increase  its  diameter, 
it  can,  on  the  other  hand,  diminish  it,  for  instance,  in  the  hyperexten- 
sion of  the  head.  In  such  cases  the  vertebrae  are  projected  forward  and 
in  SO  doing  diminish  the  anteroposterior  diameter  of  the  superior  opin- 
ing of  the  thorax,  hence  the  further  cause  of  dyspnea  (Fig.  91).  1  Ins 
would  explain  wh\  m  certain  cases  death  has  followed  exaggerated  hyper- 
extension of  the  head. 

With  young  children  flattening  of  the  windpipe  will  be  so  much  the 
more  apt  to  occur  since  in  them  the  cartilaginous  rings  of  the  trachea 
are  not  fully  developed. 


546 


THE  THYMUS  GLAND 


Pressure  in  the  Thorax. — Another  place  at  which  compression  of  the 
windpipe  may  take  place,  especially  in  adults,  is  the  point  situated 
between  the  innominate  artery  and  the  left  common  carotid  (Plate  XXX). 
This  compression  is  not  confined  to  one  ring  of  the  trachea  alone,  but 
extends  over  a  certain  portion  of  it.  This  is  easily  understood  when 
we  consider  the  anatomical  relations  of  the  thymus  to  the  trachea  in 
that  region.  Since  the  thymus  presses  on  the  anterior  surface  of  the 
trachea  in  the  space  between  the  left  common  carotid  and  the  innomi- 
nate artery,  and  since  the  trachea  lies  in  front  of  the  spinal  column, 
then  in  cases  of  sudden  enlargement  the  thymus,  being  itself  com- 
pressed between  the  spinal  column  and  the  sternum,  must  exert  a 
compression  on  the  trachea. 


Fig.  92. — Superior  opening  of  the  thorax  viewed  from  above  in  order  to  show  the  ana- 
tomical relations  of  the  thymus  with  the  other  organs  enclosed  in  "bony  ring." 


The  first  form  of  compression  which  takes  place  at  the  superior 
opening  of  the  thorax,  is  found  mostly  in  children,  while  the  second, 
or  thoracic  form,  which  takes  place  as  above  mentioned,  between  the 
innominate  artery  and  the  left  common  carotid,  is  found  mostly  in 
adults. 

Spasm  of  the  Glottis. — Inasmuch  as  the  hyperplastic  thymus  com- 
presses the  large  vessels,  namely,  the  aorta  and  the  innominate  trunk, 
and  as  we  know,  the  inferior  laryngeal  nerve  winds  around  these  vessels, 
it  will  be  easily  understood  that  these  nerves  might  become  stretched 
by  the  displacement  of  these  bloodvessels  from  the  hyperplastic  thymus 
(Plate  XXX).     We  have  already  seen  that  irritation  or  stretching  of  the 


SPASM  OF  THE  GLOTTIS  547 

inferior  laryngeal  nerve  causes  spasm  of  the  glottis,  despite  the  fact 
that  dilators  as  well  as  constrictors  of  the  glottis  are  supplied  by  the 
same  nerve,  the  inferior  laryngeal  nerve.  The  reason  lies  in  the  fact 
that  the  constrictors  of  the  glottis  being  stronger  than  the  dilators, 
irritation  of  the  inferior  laryngeal  nerve  by  stretching  must  cause  a 
spasmodic  contraction,  instead  of  a  dilatation,  and  consequently  a  spasm 
of  the  glottis.     In  such  cases  tracheotomy  would  save  the  patient. 

In  other  cases  I  believe  that  direct  pressure  on  the  base  of  the  heart 
and  consequently  on  the  heart  ganglia,  may  be  the  cause  of  death. 

In  many  instances,  however,  thymic  hyperplasia  whether  accom- 
panied or  not  by  status  lymphaticus  does  not  interfere  mechanically 
with  the  trachea,  yet  death  takes  place  sometimes  most  unexpectedly 
and  suddenlv.  I  have  in  mind  those  cases  of  sudden  death  which  take 
place  during  some  intense  nervous  excitement  such  as  coitus,  etc., 
those  of  sudden  death  just  before  or  during  anesthesia,  and  those  of 
sudden  death  following  a  cold  bath,  etc.  In  this  respect  Reckling- 
hausen's case  is  an  extremely  interesting  one.  It  was  that  of  a  boy  who 
had  fallen  from  a  boat  into  the  river,  but  was  rescued  at  once  before 
he  had  had  time  to  swallow  any  water,  yet  when  he  was  taken  out  he 
was  dead. 

In  all  these  above-mentioned  cases  the  only  pathological  findings 
were  a  thymic  hyperplasia  accompanied  or  not  by  a  status  lymphaticus, 
but  compression  of  the  windpipe  was  not  present.  What,  then,  is  the 
explanation  of  such  sudden  death  ?  Of  course  here  everything  is  still 
hypothesis.  The  fatal  issue  in  some  cases  may  be  explained  by  the 
sudden  swelling  of  the  thymus  due  to  some  exertion  such  as  in  crying, 
or  to  some  interference  with  circulation.  Possibly,  in  other  cases  the 
pressure  over  the  basis  of  the  heart,  and  especially  over  the  cardiac 
ganglia,  may  have  caused  a  sudden  inhibition  of  the  cardiac  system; 
possibly,  too,  in  certain  vulnerable  individuals  with  a  nervous  system 
in  constant  unstable  equilibrium,  the  shock  from  the  peripheral  origin 
as  was  experienced  by  falling  into  cold  water,  for  instance,  was  such  as 
totallv  to  inhibit  the  central  nervous  system.  Possibly,  too,  the  laryngo- 
tracheal reflex  caused  by  the  first  few  inhalations  of  the  anesthetic  agent 
was  powerful  enough  to  inhibit  an  already  unstable  cardiac  system. 

Most  likely,  however,  in  many  instances  the  explanation  must 
be  an  entirely  different  one,  and  we  shall  hold  the  solution  of  the 
problem  only  when  the  problem  of  internal  secretion  shall  have  been 
solved.  As  stated  before,  even  organ  contains  several  lipoids,  each 
one  possessing  a  different  physiological  property;  the  thymus  and 
lymphatic  apparatus  do  not  escape  this  rule.  In  all  marked  casts  of 
status  thymolymphaticus,  it  has  been  found  that  a  concomitanl  hypo- 
plasia of  the  chromaffin  system  and  especially  of  the  suprarenal  bodies 


54S 


THE  THYMUS  GLAND 


was  present,  hence  the  supposition  of  Wiesel  that  because  the  secretion 
of  the  suprarenal  bodies  is  insufficient  there  is  not  enough  adrenalin 
output  to  entertain  a  normal  and  constant  excitation  of  the  sympathetic 
system  which  is  an  excitatory  system;  consequently  since  the  normal 
equilibrium  between  the  sympathetic  and  vagus,  which  is  an  inhibitory 
system,  is  disturbed,  the  vagal  inhibitory  system  takes  the  upper  hand. 
These  views  are  not  all  purely  hypothetical  inasmuch  as  Neusser,  Eppin- 
ger  and  Hesse  have  shown  that  the  thymic  hormone  is  antagonistic  to 


Fig.  93 


adrenalin  and  is  vagotonic.  As  said  before,  it  has  been  shown  experi- 
mentally that  after  extirpation  of  the  thymus  there  is  a  marked  hyper- 
plasia of  the  cortical  portion  of  the  suprarenal  bodies.  Furthermore, 
we  know  that  usually  such  individuals  with  status  thymolymphaticus 
are  vagotonic;  they  perspire  freely,  their  respiratory  rhythm  is  easily 
affected,  their  blood-pressure  is  below  normal  and  their  arterial  system 
is  lypotonic. 

Diagnosis  of  Thymus  Hyperplasia. — No  matter  what  the  accepted 
explanation  may  prove  to  be,  all  our  efforts  should  be  directed  toward 
detecting  the  presence  of  thymus  hyperplasia  whether  accompanied  or 
not   by   status   lymphaticus.      In   children    the   diagnosis   is,   as   a   rule, 


DIAGNOSIS  OF   THYMUS  HYPERPLASIA 


549 


easy.  Percussion  over  the  manubrium  sterni  reveals  a  dulness  which, 
in  cases  of  marked  hyperplasia,  overlaps  on  each  side  the  ribs  and  carti- 
lages (Fig.  93).  Auscultation  over  that  region  reveals  a  prolonged 
expiration  tubular  in  character.  A  finger  placed  above  the  episternal 
notch  may  not  be  able  to  feel  the  impact  of  the  rising  thymus  during 
deglutition,    coughing,    etc.      But   the   most   certain   wav    to   detect   in 


94 


children  thymus  hyperplasia  is  given  by  the  .v-ray  1  Fig.  94):  the  shadow, 
its  form  and  location  are,  so  to  speak,  pathognomonic  and  the  diagnosis 
may  be  made  with  certainty.  In  adults,  however,  the  diagnosis  becomes 
more  difficult.  '1  he  dulness  may  be  present,  bur  ma\  be  absent,  too. 
The  shadow  of  the  mediastinal  space  may  often  be  typical,  and  allow  a 
diagnosis,  yet  sometimes  great  difficulties  arc-  encountered  in  deciding 


550  THE  THYMUS  GLAND 

whether  we  have  to  deal  with  a  thymus  hyperplasia  or  not.  One  of  my 
cases  will  illustrate  this  proposition  very  well.  My  clinical  examina- 
tion did  not  reveal  any  symptoms  pointing  toward  thymic  hyperplasia, 
consequently  I  decided  clinically  that  a  thymus  was  not  present,  yet 
the  .x-ray  showed  a  shadow  with  some  of  the  characteristics  of  thymic 
hyperplasia.  I  consequently  concluded  that  I  had  been  misled  by  my 
clinical  findings,  and  that  my  conclusions  were  erroneous.  However, 
not  long  after,  a  postmortem  showed  that  no  thymic  enlargement  was 
present. 

X-ray  Characteristics  of  Thymic  Hyperplasia. — Normally,  on  a  skia- 
gram, the  mediastinal  space  measures  from  2.5  cms.  to  3.5  cms.  under 
the  arch  of  the  aorta;  from  3  to  3.5  cms.  at  the  arch  of  the  aorta,  and 
from  5  to  6  cms.  at  the  conus  arteriosus.  The  shadow  of  this  region  is 
dark,  opaque,  regularly  distributed,  and  has  definite  limits.  But  in 
thymus  hyperplasia  there  is  a  shadow  which  overlaps  laterally  this 
mediastinal  shadow.  The  shadow  may  be  found  over  one  lobe  more 
than  over  the  other,  or  over  both  lobes  in  the  same  proportion.  The 
shadow  may  be  more  or  less  triangular  in  shape,  and  may  extend  upward 
from  the  region  of  the  auricle  in  a  straight  line  or  may  follow  to  some 
extent  the  contour  of  the  mediastinal  shadow.  Sometimes  the  region  of 
one  or  both  auricles  may  bulge  out  as  if  the  auricles  were  overdistended, 
thus  forming  an  angle  between  the  ventricle  and  the  auricle.  In  that 
case  the  base  of  the  heart  is  enlarged  and  the  enlargement  is  not  in  pro- 
portion to  the  size  of  the  heart.  The  thymic  shadow  in  some  cases  is 
superimposed  on  the  base  of  the  heart  like  a  cap  which  fits  right  over 
the  base  of  the  heart.  The  character  of  this  shadow  differs  extremely 
from  the  cardiac  and  mediastinal  shadows.  It  is  thin,  transparent,  soft, 
and  regularly  distributed  and  the  edges  are,  as  a  rule,  sharply  limited 
and  linear. 

Differential  Diagnosis  of  Thymic  Hyperplasia. — It  would  be  a  mistake 
to  believe  that  thymus  enlargement  is  the  only  cause  which  may  give 
a  congenital  stridor  and  respiratory  trouble.  Such  conditions  may  also 
be  found  with  malformations  of  the  vestibulum  of  the  larynx,  with 
tracheobronchial  glands  and  with  adenoids.  An  accurate  differential 
diagnosis  must  be  made  between  these  different  forms  of  stridor. 

The  congenital  vestibular  stridor  is  seen  after  birth.  It  is  entirely 
inspiratory  and  is  not  found  on  expiration,  except  in  rare  cases.  Cyano- 
sis is  present,  too,  but  the  stridor  and  dyspneic  symptoms  disappear 
with  intubation  of  the  larynx,  which  is  not  the  case  for  thymic  dyspnea 
in  children.  The  laryngoscopy  examination  when  possible  and  the 
autopsy  will  show  that  this  stridor  is  due  to  a  malformation  of  the 
superior  opening  of  the  larynx.  The  epiglottis  has  a  gutter  or  beak- 
like form,  and  is  folded  in  the  middle   line.     The   plicae   aryepiglotticae 


RELATION  OF  HYPERPLASIA    TO  BASEDOW'S  DISEASE      551 

of  both  sides  come  in  contact  one  with  the  other;  they  are  pulled  down 
over  the  opening  of  the  larynx  and  so  diminish  the  orifice,  hence 
dyspnea  and  stridor. 

Stridor  due  to  tracheobronchial  glands  is  found  mostly  on  expiration 
and  with  it  the  voice  has  a  bitonal  character.  Furthermore,  the  thymic 
stridor  is  congenital;  the  tracheobronchial  stridor  is  acquired.  Percus- 
sion and  radioscopy  will  reveal  entirely  different  findings. 

In  adenoids  there  may  be  difficult  and  labored  breathing  which  is 
more  noticeable  during  sleep,  but  in  such  cases  diagnosis  will  be  easv. 

Thymic  stenosis  should  not  be  mistaken  for  a  retrovertebral  abscess 
or  for  an  acute  laryngitis. 

In  laryngismus  stridulus  the  period  of  apnea  is  short,  and  respira- 
tion soon  begins  again.  During  the  intervals  it  is  usually  normal.  It 
is  always  a  manifestation  of  a  spasmogene  diathesis  and,  furthermore, 
is  always  accompanied  by  other  spasms  or  other  stigmata  (Erb's, 
Chvostek's,  and  Trousseau's  symptoms). 

Inasmuch  as  the  hyperplastic  thymus  may  come  in  contact  with 
and  compress  the  right  and  left  auricle  and  ventricle,  the  superior  vena 
cava,  the  aorta,  the  innominates,  and  the  left  common  carotid,  cyanotic 
symptoms,  characterized  by  distention  of  the  veins  of  the  neck,  bv  puffi- 
ness  of  both  supraclavicular  spaces,  and  by  cyanosis  of  the  face  and 
distention  of  the  large  fontanelle,  may  be  present.  During  paroxysm 
these  symptoms  become  extremely  marked.  The  veins  of  the  neck  are 
much  distended  and  the  fontanelle  protrudes;  the  face  is  puffed  and  the 
child  is  in  a  semicomatose  condition.  The  heart  beats  violently,  or  in 
certain  cases  stops  altogether.  When  the  paroxysm  is  over  these  symp- 
toms retrocede,  but  in  other  cases  death  ensues.  Autopsy  shows  that 
compression  of  the  right  ventricle  and  of  the  superior  vena  cava  and 
aorta  is  very  marked.  In  such  cases  the  dyspneic  symptoms  are  of 
secondary  importance.  The  vascular  symptoms  dominate  the  scene 
and  extreme  repletion  of  the  face  and  neck,  distention  of  the  large  fon- 
tanelle, and  the  tendency  to  collapse  will  differentiate  this  form  of 
cyanosis  from  the  ones  due  to  malformation  of  the  heart.  In  blue 
babies  the  cyanotic  condition  of  the  patient  is  uniformly  distributed 
and  persistent. 

Relation  of  Thymic  Hyperplasia  to  Basedow's  Disease.  For  a  long 
time  the  presence  of  thymic  hyperplasia  in  connection  with  Basedow's 
disease  was  thought  to  be  only  a  coincidence,  but  in  late  years  the  facts 
have  become  so  numerous  and  so  convincing  that  it  is  no  longer  possible 
to  deny  that  there  is  an  intimate  relation  between  the  presence  of  thy- 
mic hyperplasia  and  Graves'  disease.  Rossle  reports  a  series  of  ^2 
eases  of  hyperthyroidism  with  thymus  hyperplasia.  McCardi,  in  35 
cases  of  sudden  death  in  hyperthyroidism,  found   is  cases  with  thymic 


552 


THE  THYMUS  GLAND 


hyperplasia.  Rehn,  in  319  cases  of  Graves'  disease  treated  surgically, 
had  42  deaths.  Six  patients  died  with  extremely  marked  dyspneic 
symptoms.     In  the  literature  Matti  found  183  cases  of  hyperthyroidism 

in  which  postmortem  had  been  held, 
and  in  98  cases,  making  74  per  cent,  of 
the  total  number  of  cases,  hyperplastic 
thymuses  were  found.  Kapelle,  in  59 
postmortems  of  Basedow  cases,  found 
that  thymic  hyperplasia  was  present 
in  79  per  cent,  of  the  cases.  These 
figures  show  that  thymic  hyperplasia 
in  combination  with  Graves'  disease, 
is  very  frequent.  I  have  reported  sev- 
eral cases  of  thymic  hyperplasia  and 
Basedow's  disease  corroborated  by 
postmortem  (Fig.  95). 

The  importance  of  such  facts  is 
great,  and  whenever  it  is  possible  the 
probable  presence  of  thymic  hyper- 
plasia should  be  ascertained  before 
attempting  thyroidectomy  or  at  the 
time  of  the  operation.  Remarkable, 
and  somewhat  disconcerting,  is  the 
fact  that  thymus  hyperplasia  is  very 
much  less  apt  to  be  found  in  very 
severe  and  protracted  cases  of  Graves' 
disease  than  it  is  in  the  earlier  forms. 
Already  in  1908  Hart  came  to  the 
conclusion  that  besides  a  thyroid  Base- 
dow there  could  be  such  a  thing  as  a 
thymus  Basedow,  the  latter  form  being 
characterized  by  the  same  cardinal 
symptoms  as  those  seen  in  thyroid 
Basedow.  These  views  have  been  up- 
held by  Kappelle,  Bayer,  Bircher,  and 
Klose.  Bircher  reproduced  experimen- 
tally in  dogs  a  Basedow's  disease  by 
injecting  thymus  products  into  the 
peritoneal  cavity;  tachycardia,  nerv- 
ousness, tremor,  exophthalmos,  were 
Fig.   95. — Thymic    hyperplasia    and  T  ,  ,     , 

„      ,     ,    ,.  present.     1  have  repeated  these  exper- 

rJasedow  s  disease,  a  postmortem  speci-      r  r  r 

men.  Note  that  the  thymus  covers  the  iments  several  times,  and  although  I 
heart  entirely.  was  not  able  to  obtain  the  symptoms 


THYMOGEXE  BASEDOW  553 

with    the    same    intensity    as    Bircher,  yet  I  was    able  to  see  the  same 
cardinal  symptoms  moderately  developed. 

Lately  Svehla  has  asserted  that  the  thymus  gives  off  an  internal 
secretion,  and  thinks  that  death  is  due  to  this  substance  acting  on  the 
heart  and  nervous  system.  By  injecting  a  watery  solution  into  animals, 
Svehla  found  a  diminution  in  the  blood-pressure  and  increased  rapidity 
of  the  pulse.  Repeated  injections  caused  the  death  of  the  animals; 
therefore  he  considers  the  mors  thymica  as  a  consequence  of  hyperthy- 
mization  resulting  in  a  diminution  of  the  blood-pressure. 

There  is  unquestionably  a  synergic  action  between  the  thyroid  and 
the  thymus;  one  activates  the  other,  and  vice  versa.  This  seems  to  be 
demonstrated  bv  cases  of  Basedow's  disease  where  surgical  interference 
on  the  thyroid  did  not  give  the  expected  results,  but  where  the  cure  was 
secured  most  rapidly  and  most  completely  by  adding  to  it  the  removal 
of  the  thymus.  Such  cases  have  been  shown  by  Garre,  Kapelle  and 
Barer.  Von  Haberer's  case  in  that  respect  is  most  instructive.  The 
patient  was  a  man  suffering  with  the  most  intense  hyperthyroidism 
accompanied  by  marked  choking  spells.  Ligation  and  thyroidectomy 
were  performed  br  eminent  surgeons,  one  of  them  none  other  than 
Kocher,  ret  the  improvement  of  the  patient  was  only  slight  and  tem- 
porary, so  that  he  soon  fell  back  into  a  pitiful  condition  which  was  con- 
sidered hopeless.  Besides  the  thyrotoxic  symptoms  the  dyspnea  wTas 
intense  and  the  condition  of  the  heart  was  so  bad  that  death  was  looked 
for  at  anr  time.  Von  Haberer  decided  to  attempt  the  removal  of  the 
thrmus,  but  at  the  operation  was  very  much  disappointed  to  find  no 
trace  of  thrmus;  all  that  he  was  able  to  remove  was  a  small  piece  of  fat 
which,  nevertheless,  proved  under  microscopic  examination  to  contain 
some  thymus  gland.  From  the  time  of  this  operation  on,  the  improve- 
ment of  the  patient  was  so  marvelous  that  he  recovered  rapidly  and 
entirely. 

Thymogene  Basedow. — We  may  say,  consequently,  that  the  majority 
of  cases  of  Graves'  disease  are  of  thyroid  origin,  but  that  their  intensity 
may  be  increased  by  a  concomitant  thymic  hyperplasia.  In  other  words, 
the  deleterious  effects  of  the  two  glands  sum  each  other  up;  consequently 
the  presence  of  a  thymic  hyperplasia  in  Graves'  disease  must  always  be 
looked  for,  and  must  always  he  regarded  as  a  complication.  We  may, 
furthermore,  admit  that  we  may  have  some  eases  of  Graves'  disease  of 
purely  thymic  origin,  as  we  have  cases  of  Graves'  disease  of  purely 
thyroid  origin.     Finally,  we  may  have  both  forms  combined. 

Differential  Diagnosis  between  Thymic  and  Thyroid  Basedow.  It  all 
these  conditions  are  true,  it  will  then  be  necessary  to  ascribe  to  ever} 
case  of  Graves'  disease  its  true  origin.  In  other  words,  we  shall  have 
to  decide  if  we  have  to  deal  with  a  thyroid,  or  a  thymic,  Basedow,  or  a 


554  THE  THYMUS  GLAND 

mixed  one.  Let  it  be  said  right  now  that  in  the  greatest  number  of 
cases  we  shall  have  to  deal  with  a  thyroid  Basedozv.  This  form,  however, 
may  be  combined  with  the  thymic  Basedow.  The  pure  form  of  thymic 
Basedow  is  rare. 

How  are  we  going  to  differentiate  these  two  forms  ?  As  was  seen  in 
the  chapter  on  Basedow's  Disease,  in  many  cases  there  is  a  certain  group 
of  symptoms  which  seem  to  be  more  dependent  upon  the  excitation  of 
one  of  the  two  nerves  of  vegetative  life,  the  vagus  and  the  sympathetic. 
If  the  predominating  symptoms  are  of  vagus  origin,  the  case  is  called 
vagotonic.  If,  on  the  other  hand,  the  predominating  symptoms  are  of 
sympathetic  origin,  the  case  is  called  sympatheticotonic.  We  have  seen, 
too,  that  according  to  Eppinger  and  Hesse,  the  vagotonic  symptoms  are: 

i.  A  moderate  degree  only  of  tachycardia,  but  intensely  marked 
subjective  symptoms. 

2.  A  marked  Graefe  symptom  with  pronounced  enlargement  of  the 
eyelids,  accompanied,  however,  by  a  moderate  exophthalmos,  but  with 
no  Moebius.    The  lachrymal  secretion  is  increased. 

3.  Profuse  perspiration. 

4.  Diarrhea,  hyperacidity,  vomiting. 

5.  Increased  eosinophilia. 

6.  Alimentary  glycosuria. 

According  to  the  same  authors  the  sympatheticotonic  symptoms 
are: 

1.  A  marked  exophthalmos  but  no  Graefe;  with  positive  Moebius; 
and  with  suppressed  lachrymal  secretion. 

2.  Pronounced  tachycardia,  however,  with  only  moderate  subjective 
symptoms. 

3.  No  perspiration,  no  diarrhea,  no  vomiting. 

4.  Marked  falling  of  the  hair. 

5.  No  eosinophilia,  no  alimentary  glycosuria. 

6.  Occasionally  a  slight  increase  in  temperature. 

According  to  Eppinger  and  Hesse  the  vagotonic  symptoms  are  pro- 
duced by  a  thymic  hormone  which  would  act  as  an  excitant  of  the  vagal 
system.  It  is  not,  however,  demonstrated  beyond  all  doubt  that  all 
the  symptoms  considered  as  vagotonic  are  really  of  such  origin.  The 
same  is  true  for  the  sympatheticotonic  symptoms.  There  will  be  needed 
further  work  in  order  to  throw  light  upon  that  subject. 

So  far  the  true  thymogene  Basedow  is  still  difficult  to  diagnose 
beforehand.  As  a  rule  this  diagnosis  is  made  only  retrospectively  after 
the  thyroid  has  been  removed,  and  after  it  is  found  that  the  micro- 
scopic examination  does  not  show  the  typical  microscopic  changes  in 
the  thyroid  known  as  pathognomonic  of  the  disease,  and  after  one  sees 
that  the  clinical  results  do  not  come  up  to  the  expectations;  only  then 


TREATMENT  OF  THYMIC  HYPERPLASIA  555 

the  idea  of  a  thymic  Basedow  dawns  upon  one's  mind.  Unfortunately, 
the  ff-rays  as  a  diagnostic  means  in  adults  have  not  proved  as  useful  as 
I  thought  they  would.  In  a  series  of  several  hundred  goiters  of  all 
kinds,  I  have  systematically  made  a  Roentgen  examination.  In  many 
instances  I  was  able  to  demonstrate  beforehand  the  presence  of  an 
enlarged  thymus,  but  others  in  which,  according  to  the  radiograms,  no 
thymus  was  present,  I  was  very  much  surprised  to  find  at  the  time  of 
the  operation  quite  an  important  thymic  enlargement.  A  symptom 
which  I  think  is  of  good  diagnostic  value  in  diagnosing  thymic  hyper- 
plasia complicating  a  Basedow  case,  is  marked  muscular  asthenia. 
Furthermore,  the  presence  of  small  lymph  nodes  in  the  cervical  region 
must  be  regarded,  in  my  judgment,  as  a  strong  presumption  in  favor  of 
the  presence  of  thymic  hyperplasia;  in  fact,  the)'  belong  to  the  status 
thymolymphaticus. 

Lymphocytosis  has  been  the  subject  of  much  discussion.  It  was  at 
first  considered  as  of  thyroid  origin,  but  lately  the  number  of  research 
workers  is  constantly  increasing  who  seem  to  be  inclined  to  believe  that 
lymphocytosis  is  due  to  thymic  hyperplasia. 

In  conclusion  I  believe  that:  Although  the  question  is  far  from  being 
settled,  nevertheless  a  high  lymphocytosis  with  moderate  enlargement 
of  the  thyroid;  a  moderate  tachycardia,  but  with  intense  subjective 
symptoms;  the  presence  of  small  cervical  lymph  nodes;  an  increased  area 
of  dulness  over  the  manubrium  sterni;  a  prolonged  expiration  over  this 
area  with  a  character  which  is  truly  tubular;  all  these  symptoms  together 
with  a  positive  .v-ray  are  strongly  suspicious  of  a  thymic  hyperplasia. 

Treatment  of  Thymic  Hyperplasia  Complicating  Graves'  Disease. — 
From  what  has  been  stated,  it  follows  that  thymic  hyperplasia  in  goiter 
surgery  can  no  longer  be  disregarded.  It  is  a  serious  complication  which 
occurs  not  only  in  Graves'  disease,  but  in  simple  goiter  also.  It  is  liable 
to  kill  the  patient  either  by  choking  him,  or  by  causing  a  thymic  intoxi- 
cation leading  to  hyperthyroidism,  hyperthymism,  and  possibly  to 
acidosis.  What  shall  we  do  then  ?  Simply  remove  the  thymus.  Sim- 
ply combine  thymectomy  with  thyroidectomy.  And  that  is  just  what  1 
have  been  doing  in  the  past  few  years  in  every  goiter  case  that  has  come 
my  way.  In  every  case  as  soon  as  thyroidectomy  is  terminated,  1 
explore  systematically  the  mediastinum  and  whenever  thymus  is  found, 
it  is  removed.  In  so  doing,  not  only  the  remote  results  are  better,  but 
the  postoperative  course  is  also  far  more  satisfactory.  First  of  all,  the 
possibility  <>f  a  mechanical  thymic  death  is  eliminated,  and  this,  cer- 
tainly, is  a  great  relief.  Always  before  tins,  after  a  thyroidectomy,  I 
felt  exceedingly  uneasy  and  anxious  for  twenty-four  hours  because  at 
any  time  a  choking  spell  was  liable  to  occur.  1  here  are  no  more  such 
fears  for  me  now. 


556  THE  THYMUS  GLAND 

Furthermore,  the  postoperative  reaction  which  so  often  follows  an 
operation  for  goiter,  but  especially  the  thyrotoxic  one,  is  unmistakably 
better;  temperature  is  not  so  high;  nervousness  is  not  so  extreme;  delir- 
ium is  far  less  marked;  acidosis  is  less  severe  and  what  is  more  the  death- 
rate  is  certainly  less.  All  told,  I  consider  this  combined  operation  a 
great  step  forward  in  the  surgical  treatment  of  Graves'  disease. 

Treatment  of  Thymic  Hyperplasia  in  Children. — In  cases  of  thymic 
hyperplasia  in  children,  if  the  mechanical  symptoms  are  alarming,  I 
operate  at  once.  What  is  the  use  of  running  the  risk  of  losing  the  little 
patient  by  trying  any  other  method  of  treatment  when  the  operative 
treatment  is  still  safe  ?  Two  of  my  cases  which  had  a  marked  thymus 
hyperplasia  and  in  which  the  thymus  compressed  not  only  the  trachea 
but  also  the  esophagus,  gained  an  ounce  the  same  day  that  thymectomy 
was  performed,  and  continued  to  do  so  for  two  weeks  after;  in  three 
months  the  two  little  patients  had  become  prosperous  and  healthy. 
Several  others  who  had  choking  spells  increasing  constantly  in  intensity, 
so  much  so  that  when  brought  for  operation  they  were  between  life  and 
death,  as  soon  as  thymectomy  was  performed,  soon  breathed  regularly 
and  regained  perfect  health. 

If,  however,  operation  cannot  be  performed  because  of  impending 
death,  intratracheal  rubber  tubes  should  be  introduced,  either  through 
the  larynx  or  through  a  tracheotomy  opening.  It  is  important  to  make 
sure  that  the  tube  opens  at  the  end  and  not  on  the  side.  It  is  important, 
too,  to  extend  the  tube  well  into  the  trachea  so  as  to  pass  the  point  of 
compression.  We  must  remember,  however,  that  tracheotomy  ought  to 
be  resorted  to  as  a  last  measure,  because  we  know  by  experience  that 
tracheotomy  combined  with  thymectomy  is  usually  fatal  on  account  of 
postoperative  bronchopneumonia,  and  especially  mediastinitis. 

If  the  choking  spells  are  not  alarming,  x-ray  treatment  is  the  method 
of  choice. 


PLATE   XXX II 


> 


-# 


Thymectomy. 

After  the  sternohyoid  and  the  sternothyroid  muscles  have  been  separated  in  the 
middle  line  and  reclined,  a  more  or  less  round  mass  is  often  seen  bulging  upward  with 
each  expiration  and  disappearing  again  with  each  inspiration.     That  is  the  thymus. 


FIG.  2 


Thymectomy. 

If  the  thymus  is  grasped  between  two  forceps  and  its  capsule  cut,  the  thymic  paren- 
chyma bulges  <>ur  as  if  under  pressure,  especially  with  each  expiration. 


CHAPTER    LI  I. 

SURGICAL  TECHNIC  OF  THYMECTOMY. 

Anesthesia. — In  adults  it  is  self-evident  that  almost  invariably 
thymectomy  should  be  performed  under  anesthesia.  In  children,  espe- 
cially in  newborn,  the  dyspnea  may  be  so  intense  that  anesthesia,  no 
matter  what  form,  may  only  increase  the  dyspnea,  consequently  in 
such  conditions  the  operation  may  have  to  be  performed  under  local 
anesthesia  or  without  anesthesia  at  all,  as  in  newborn  for  instance.  In 
the  great  majority  of  cases,  however,  it  is  better  to  resort  to  complete 
anesthesia,  as  the  crying  from  pain  will  only  increase  the  congestion  of 
the  thymus  and  consequently  increase  the  dyspnea.  In  small  children 
chloroform  seems  to  be  preferable  to  ether. 


M.  mylohyoideus 
Os  Viyoideuan 


"Plafysma. 


M.  sterjw-hyoideus 
Storna-cloido-mciAtoidei 


_    _M.  stei'nO- 

Inyreoideus 


Fig.  96. — Anatomv  of  the  muscles  involved  in  performing  thymectomj 


Surgical  Technic.  1.  A  short  transverse  incision  is  made  just  above 
the  manubrium  sterni.  The  skin  is  cut  and  the  two  Maps  are  retractedj 
one  upward  and  the  other  downward. 

2.  The  superficial  cervical  fascia  is  clamped  between  two  forceps  and 

CUt  in  the  middle  line.      (Plate  \X.\1,  Fig.  1.) 


558  SURGICAL  TECH  NIC  OF  THYMECTOMY 

3.  The  prethyroid  muscles  are  separated  in  the  middle  line  and 
retracted  laterally.     (Plate  XXXI,  Fig.  2.) 

4.  After  the  sternohyoid  and  the  sternothyroid  muscles  have  been 
separated  in  the  middle  line  and  retracted,  one  often  sees  a  more  or  less 
round  mass  bulging  upward  with  each  expiration  and  disappearing  again 
with  each  inspiration.  That  is  the  thymus.  (Plate  XXXII,  Fig.  1.)  In 
children,  and  sometimes  in  adults,  the  hyperplastic  thymus  reaches  the 
lower  pole  of  the  thyroid  so  it  is  easily  discovered. 

5.  The  thymus  is  then  clamped  between  two  hemostats  and  pulled 
gradually  upward.  Great  care  should  be  taken  in  clamping  every  bit 
of  loose  tissue  around  the  capsule  of  the  thymus  so  as  to  catch  every 
small  vessel. 

In  the  great  majority  of  cases  resection  of  the  thymus  is  better  made 
extracapsularly,  as  usually  the  thymus  is  easily  loosened  from  the  sur- 
rounding structures.  Whenever,  however,  there  is  some  perithymitis 
and  consequently  there  is  some  difficulty  in  getting  the  thymus  up,  it  is 
better  then  to  perform  an  intracapsular  thymectomy  as  shown  in  Plate 
XXXII,  Fig.  2.  The  glandular  capsule  of  the  thymus  is  then  opened  and 
as  soon  as  this  is  done  the  thymic  parenchyma  bulges  out  as  if  under 
pressure,  especially  with  each  expiration.  The  parenchyma  is  then 
shelled  out  slowly,  gradually,  and  more  or  less  easily.  As  said  before, 
however,  at  least  in  my  experience,  the  extracapsular  method  is  the  one 
of  choice,  provided  one  takes  a  great  deal  of  pains  to  clamp  every  par- 
ticle of  loose  connective  tissue  in  connection  with  the  thymus.  In  the 
numerous  thymectomies  which  I  have  performed,  I  have  never  met 
with  an  unpleasant  hemorrhage  following  this  mode  of  operating. 

6.  When  sufficiently  isolated  the  thymus  is  then  ligated  snugly  at 
its  basis  (Plate  XXXIII,  Fig.  1)  in  order  to  catch  the  few  thymic  vessels 
which  supply  the  gland  and  it  is  cut  far  enough  from  the  ligation  to 
prevent  the  ligature  from  slipping.  If  this  should  happen,  a  hemorrhage 
almost  impossible  to  check  except  by  packing  will  occur. 

7.  After  all  ligations  of  the  clamped  vessels  have  been  performed, 
the  prethyroid  muscles  are  sewed  up  again  in  the  middle  line  by  run- 
ning suture  or  by  one  or  two  interrupted  stitches.  (Plate  XXXIII.) 
1  he  subcutaneous  tissue  and  platysma  are  sewed  up  by  continuous 
running  suture,  and  intradermic  suture  is  performed. 


PLATE   XXXIII 


FIG.    1 


:«# 


Thymectomy. 

When  isolated,  the  thymus  is  ligated  snugly  at  its  basis  in  order  to  catch  the  few 
thymic  vessels  and  it  is  cut  far  enough  so  as  to  prevent  the  ligature  from  slipping, 
thus  causing  a  hemorrhage  almost  impossible  to  check  except  bv  packing. 


FIG.   2 


J* 


Thymectomy. 

'I  he  prethyroid  vessels  art'  then  sewed  together  in  the  middle  line,  subcutaneous 
tissue  is  sutured  by  itself  and  intradermic  suture  is  performed. 


INDEX 


Acapnia,  511 
Accidents,  operative,  478 
Acidosis,  521 
Adenocarcinoma,  67 
Adenoma,  fetal,  57,  64 

malignant,  67 
Adrenalin,  chloride,  502 

opotherapy,  428 
Adrenalinemia,  353 
Adrenals,  390 
Air  embolism,  481 
Albuminuria,  358 
Anatomical  facts  of  thyroid,  440 

conclusions  from,  448 
Anatomopathological  relations  of  goiter,  1 1! 
Anatomy,  17 

pathological,  1 15 
Anesthesia,  494,  557 

general,  495,  498 

intratracheal  insufflation,  506 

local,  495,  498,  501 

technic  of,  502 
Antithyroid  chymotherapy,  426 
Antitoxic  action  of  thyroid,  53 
Antitrypsin  content  of  blood,  354 
Aortic  goiter,  87 
Aphonia,  344 
Appetite,  340 
Arginine,  38 
Vrsenic,  287 

in  thyroid,  50 
Artery,  ima,  20 

inferior  thyroid,  20,  125,  462 

parathyroid,  446 

superior  thyroid,  [9,  124,  462 
Athyroidism,  congenital,  i<;o,  203 
differential  diagnosis,  210 

(I  iologV   of,   203 

opotherapy  in,  2SS 
s\  mptoms,  207 
surgical,  i«>o,  196 

opotherapy  in,  2XS 
S3  mptoms  of,  [96 


B 


Ham  dow  iodin,  $93 
struma,  311 


Basedow    thymic   and  thyroid,   differential 
diagnosis  of,  553 
thymogene,  553 
thymus,  552 
thyroid,  552 
Basedowified  goiter,  311,  312,  434 
Basedow's  disease,  303.       See  Graves'    dis- 
ease, 
relation  of  thymic  hyperplasia    to, 

551. 
thyroiditis  and,  396 
Benign  goiter,  58 
Blood,  antitrypsin  content  of,  354 

changes,  349 

coagulability  of,  352 

deficiency  of  carbon  dioxide  in,  511 

pressure,  3  10 

supply,  19.  442 
Bloodvessels,  relation  of  goiter  to,  124 
Bodies,  postbranchial,  27 
Breath,  shortness  of,  343 


Cachexia  strumipriva,  182,  189,  190 

surgical,  196 

symptoms  of,  196 

thyreopriva,  31,  183.  189,  190 
Cancer,  65,  66 

aneurysmal,  176 
course  and  symptoms  of.  175 
diagnosis  of,  178 
treatment  of,  179 
Cancroid.  76 
Canthorraphy,  487 

Carbon  dioxide,  deficiency  of,  in   blood.  ;ii 
Carcinoma,  70 

sarcomatodes,  So 
Cardiac  spasm,  ? '  • 
Cardiopathic  goiti  r,  133 
Cardiovascular  symptoms,  303,  304 
Chemistry,  biological,  42,  405,  514 
Chloroform,  1.98,  1.99 
Choking  spells,  thj  mic,  343 
Chorea,  }?S 

Ch\  ostek  symptom,  525 
( 'In  motherapy,  antii nj  roid,  \-<< 
Circular  goit<  r,  122,  [63 

diagm  isis  of,  1 63 

s\  mptoms  of,  1 '  1 


560 


INDEX 


Circular  goiter,  treatment  of,  164 
Cleavage,  pathological  planes  of,  442 
Coagulability  of  blood,  352 
Collapse  of  trachea,  479 
Colloid,  22 

desquamation  of,  23 

goiter,  57,  61,  166 
diffuse,  62 
Congenital  goiter,  166 

symptoms  of,  167 
treatment  of,  168 
Constipation,  341 
Contagion  by  contact  theory,  265 
Coughing,  344 
Cretinism,  203 

differential  diagnosis  of,  210 

economical  significance  of,  227 

endemic,  189,  190 

etiology  of,  204,  220 

fluctuations  of,  234 

geographical  distribution  of,  221 

military  significance  of,  227 

opotherapy  in,  endemic,  289 

social  significance  of,  227 

sporadic,  190 

symptoms  of,  207 
Cretinoids,  21 1 

Crotti's  formulae  for  non-toxic  parenchyma 
tous  goiter,  281 
for  exophthalmic  goiter,  428 

technic  of  indirect  transfusion,  518 

treatment  for  exophthalmic  goiter,  428 
for  non-toxic  parenchymatous  goi- 
ter, 281 
Cutaneous  symptoms,  347 
Cyst,  false,  62 

hydatid,  1 13 

median,  83 

true,  62 
Cystic  goiter,  166 


D 


Dallrymple  symptom,  319,  322 
Danger  zone,  441,  442,  448,  462,  471 
Deaf- mutism,  223 
Death,  goiter,  162 
sudden,  300 
thymic,  545 
Delirium,  acute,  336 
Dermographism,  347 
Dermoids,  59,  81 
Desquamation  of  colloid,  23 
Diabetes,  356 

Diagnosis  of  circular  goiter,  163 
differential,  of  cancer,  178 

of  congenital  athyroidism,  210 
of  cretinism,  210 
of  intrathoracic  goiter,  155 
of  spontaneous  infantile  hypothy- 
roidism, 210 


Diagnosis,    differential,    of   thymic    hyper- 
plasia, 550 
and  thyroid  Basedow,  553 
of  thyrotoxic  tachycardia,  304 

of  goiter,  130 

of  intrathoracic  goiter,  152 

of  malignant  goiter,  178 

of  strumitis,  98 

of  thymic  hyperplasia,  548 

of  thyroiditis,  98 
Diarrhea,  341 
Diet,  420 

Diffuse  goiter,  57,  58 
Digestive  disturbances,  339 
Disease,  Basedow's.     See  Graves'  disease. 

thyro-neuro-polyglandular,     372,     393, 
403 
Duct,  lingual,  25 

thymopharyngeal,  537 

thyroid,  25 
Dysphagia,  127 
Dyspnea,  126 
Dyspneic  symptoms,  313 
Dysthyroidism,  370,  401 


E 


Edema  of  eyelids,  325 
Electrotherapy,  421 
Embolism,  air,  481 
Embryology,  23 
Emotionality,  334,  336 
Endothelioma,  79 
Enucleation,  448,  450,  453 
Enucleoresection,  453 
Epidemics,  goiter,  228 
Epithelial  neoplasms,  65 
Erb  symptom,  528 
Esophagus,  injury  to,  481 

relation  of  goiter  to,  123 
Ether,  498,  499 
Etiology  of  congenital  athyroidism,  203 

of  cretinism,  204,  220 

of  exophthalmos,  326 

of  goiter,  endemic,  220 

theories  regarding,  341 

of  Graves'  disease,  370 

of  hypothyroidism,  198 

of  infantile  hypothyroidism,  204 

of  spontaneous  adult  hypothyroidism, 
289 

of  strumitis,  93 

of  thyroiditis,  93 
Excision,  448,  449 
Exhaustion,  vasomotor,  509 

suprarenal,  512 
Exophthalmic  goiter,  60,  303 

Crotti's  treatment  for,  428 
eyelid  symptoms  in,  322 
in  pregnancy,  367 

treatment  of,  368 


IXDEX 


561 


Exophthalmos,  303,  319 
bilateral,  320 
etiology  of,  326 
unilateral,  319 

Exothyropexy,  374 


Fibrosarcoma,  77 
Fibrous  goiter,  63 
Flatulence,  340 


Ganglion  cells,  morphological  changes  in, 

51.1 

Genital  apparatus,  105 

disturbances,  342 
system,  389 
Glands,  accessory,  27 
Glottis,  spasm  of,  546 
Glycogen-containing  goiter,  72 
Glycosuria,  356 
Goiter,  accessor}',  27,  59,  82 

anatomopathological  relations  of,  118 

and  radio-active  waters,  262 

in  animals,  236 

aortic,  87 

Basedowified,  311,  312,  434 

benign,  58 

cardiopathic,  133 

in  children,  169 

circular,  122,  163 

diagnosis  of,  163 

symptoms  of,  163 

treatment  of,  164 
clinical  symptoms  of,  126 
colloid,  57,  61,  166 
congenital,  166 

symptoms  of,  167 

treatment  of,  168 
Crotti's  treatment  for,  281 
cystic,  166 
death,  160 

diagnosis  of,  130 
diffuse,  57,  58 

colloid,  62 

nodular,  62 
dislocation  of,  471 
endemic,  economical  significance  of,  227 

etiology  of,  220 

fluctuations  of,  232 

geographical  distribution  of,  -21 

military  significance  of,  287 

social  significance  of,  227 

water  and,  242 

epidemics,  228 

exophthalmic,  60,  203 

(Yoi  ti's  treatmeni  for,  42K 
eyelid  symptoms  in,  t,zz 
36 


Goiter,  exophthalmic,  in  pregnancy,  367 
treatment  of,  368 
fibrous,  63 

glycogen-containing,  72 
heart,  mechanical,  133 

thyrotoxic,  136,  307 
heredity-  in,  248 
intrathoracic,  240 

accessor}',  186 

diagnosis,  152 

differential,  155 

operation  for,  475 

prognosis  of,  159 

relation  to  neighboring  tissues,  142 

symptoms  of,  143 
intratracheal,  165 
lingual,  85 
malignant,  58,  65 

clinical  aspects  of,  173 

course  and  symptoms  of,  175 

diagnosis  of,  178 

forms  of,  80 

relation  to  structures,  178 

technic  of  operation  for,  477 

treatment  of,  179 
mechanical  symptoms  of,  126 
median,  122 
metastatic  colloid,  70 
nodular,  57,  58,  119 

colloid,  62 

relation  to  bloodvessels,  124 
non-toxic  vascular,  63 
ovarian,  87 
parenchymatous,  57,  60,  166,  167 

diffuse,  118 
pendulous,  1 19 
plunging,  141,  160 
postbranchial,  73 
proliferating,  67 
pyramidal,  122 
relation  to  larynx  and  trachea,  120 

to  nerves,  125 

to  pharynx  and  esophagus,  123 

to  skin  and  muscles,  119 
retro-esophageal,  175 
retrotracheal,  [65 
simple,  indications  for  operation,  295 

medical  treatment,  276,  277 

pregnancy  and,  175 
t  rear  men  t  of,  171 
thyrotoxic,  consistency  of,  312 

histology  of,  315 

pathology  of,  315 

surface  of,  313 

\  olume  of,  5 1  _ 
\  ascular,  58,  63,  166 
( Iraefe  S3  mptom,  }  10.  322 
( irafting  of  parai In  roids,  532 

of  thyroid,  291 
( Iraves'  disease,  .unit-  delirium  in,  336 

adrenalin  in,  428 

adrenalinemia  in,  5  5  j 


562 


INDEX 


Graves'  disease,  albuminuria  in,  358 

antitrypsin  content  of  blood  in,  354 

appetite  in,  340 

blood  changes  in,  349 

brown  pigmentation  of  skin  in,  348 

chorea  in,  338 

coagulability  of  blood  in,  352 

constipation  in,  341 

coughing  in,  344 

Crotti's  treatment  for,  428 

cutaneous  symptoms  in,  347 

Dallrymple  symptom  in,  322 

dermographism,  347 

diabetes  in,  356 

diarrhea  in,  341 

diet  in,  420 

digestive  disturbances  in,  339 

disturbances  in  metabolism  in,  355 

edema  of  eyelids  in,  326 

electrotherapy  in,  421 

emotionality  in,  334,  336 

etiology  of,  370 

eyelid  symptoms  in,  322 

falling  of  hair  in,  348 

flatulence  in,  340 

fulminating  forms  of,  358,  436 

genital  disturbances  in,  342 

giving  away  of  knees  in,  331,  333 

glycosuria,  356 

Graefe  symptom  in,  322 

headache  in, 345 

heredity  in,  338 

hoarseness  in,  344 

hydrotherapy  in,  421 

hyperglycemia  in,  354 

hyperh)  drosis  in,  347 

hypophysis  in,  428 

hysteria  in,  336 

indications  for  surgical  treatment, 

.430 

insomnia  in,  345,  346 

instability  in,  334,  335,  336 

irritability  in,  344,  336 

is  a  medicosurgical  disease,  438 

is  a  toxic  thyroiditis,  399,  404 

itching  of  skin  in,  347 

Kocher  symptom  in,  323 

lachrymal  secretion  in,  325 

leukopenia  in,  349,  350 

loss  of  flesh  in,  355 

medical  treatment  for,  407,  417 

medication  in,  419 

mental  symptom  in,  334 

Moebius  symptom  in,  324 

muscular  cramps  in,  333 
fatigue  in,  332 
symptoms  in,  331 

nausea  in,  340 

nervous  origin  of,  382 
symptoms  of,  334 

neurasthenia  in,  337 

numbness  in,  346 


Graves'  disease,  ocular  symptoms  in,  319 
pains  in,  345 

pancreas  opotherapy,  428 
parathyroid  opotherapy,  428 
pathological  arguments,  375 
polydipsia  in,  358 
polyglandular  medication  in,  427 

origin  of,  388 
polyuria  in,  357 
radiotherapy  in,  422 
respiratory  disturbances  in,  343 
rest  cure  for,  417 
restlessness  in,  334,  335,  336 
results  of  medical  treatment,  408 
sensations  of  heat  in,  347 
sensory  disturbances  in,  345 
serotherapy  in,  426 
shortness  of  breath  in,  343 
staring  look  in,  325 
Stellwag  symptom  in,  324 
temperature  in,  355 
tendinous  reflexes  in,  333 
tingling  in,  346 
treatment  of,  405 

for  each  case,  434 

of  thymic  hyperplasia  compli- 
cating,  555 
tremor  in,  331 
thymus  opotherapy  in,  328 
thyrogenetic  origin  of,  372 
thyrotoxic  symptoms  in,  359 
urticaria  in,  348 
vertigo  in,  346 
vomiting  in,  340 
when  cured?,  415 


H 


Hair,  falling  out  of,  348 

Headaches,  345 

Heart,  mechanical  goiter-,  133 

test  of  functional  capacity  of,  310 

thyrotoxic  goiter-,  136,  307 
Heat,  sensations  of,  347 
Hematoma,  postoperative,  534 
Hemorrhage,  treatment  of,  515 
Hemostasis,  466 
Heredity  in  goiter,  248 

in  Graves'  disease,  338 
Histology  of  goiter,  21 

of  thyrotoxic  goiter,  315 
Hoarseness,  344 
Hydrotelluric  theory,  249 
Hydrotherapy,  421 
Hyperhydrosis,  347 
Hyperlymphocytosis,  349 
Hypersecretion,  370 
Hyperthyroidism,  303,  363,  370,  372,   400, 

434  . 
fruste  forms  of,  360,  437 
infantile,  365 


IXDEX 


563 


Hyperthyroidism,  juvenile,  365 
postoperative,  519 
small,  360 
Hypertrophy,  thyroid,  303 
Hypoglycemia,  354 
Hypophysis,  55,  195 
in  opotherapy,  428 
in  thyroid,  389 
Hypopolynucleosis,  349,  350 
Hypothyroidism,  51,  182,  190,  363,  372,  417 
etiology  of,  198 
fruste  forms,  190 
relationship  of  forms  of,  187 
spontaneous,  190 
adult,  198 

opotherapy  of,  289 
symptoms  of,  200 
infantile,  203 

differential  diagnosis  of,  210 
etiology  of,  204 
opotherapy  of,  288 
symptoms  of,  207 
surgical,  190 
Hysteria,  336 


Icterus,  341 
Idiocy,  188,  189,  203 

with  pachydermic  cachexia,  189 
Incision,  469 

low  collar,  469 
Infection  theory,  272 
Inflammations,  59 
Ingestion  method  of  treatment,  285 
Inhibition  of  the  function  of  organs,  511 
Injections,  boiling-water,  487 

technic  of  boiling  water,  488 
treatment  with,  300 
Injury  to  trachea,  esophagus,  and   pleura, 

481 
Insomnia,  345,   546 
Instability,  334,  335,  336 
Insufficiency,  to  prevent  thyroid,  41 

treatment  of  thyroid,  283 
Insufflation,  intratracheal,  506 
Internal  secretion,  55 

functional  interrelation  of  organs  of,  55 
Intrathoracic  goiter,  140 
accessory,  86 
diagnosis  of,  1 52 

differential,  1  55 
opera  nun  for,  475 
prognosis  of,  1 59 

r<  la t ion  to  neighboring  tissues.  14: 
s\  mptoms  of,  1 43 
Intratracheal  goiter,  165 
lodin- Basedow,  593 

medication,  dangers  of,  282 

in  tin  roid  gland,  44 

in  treatment  of  goiter,  271; 


Iodism,  constitutional,  393 
Iodothyreoglobuhn,  42,  52 
Irritability,  334,  336 
Isthmus,  17 
Itching  of  skin,  347 


K 


Katzenstein  test,  310 
Knees,  giving  way  of,  331,  333 
Kocher-Reverdin  controversy,  182 
Kocher  symptom,  319,  323 


Lachrymal  secretion,  325 
Laryngoscopic  examination,  131 
Larvnx,  relation  of  goiter  to,  120 
Lesions  of  the  nerves,  478 
Leukopenia,  349,  350 
Ligaments,  suspensory,  19 

thyrothymic,  538 
Ligation,  458 

indications  for,  460 

intracapsular,  462 

isolated,  of  inferior  thyroid  arterv,  464. 

465 
of  superior  pole,  464 
point  of  election  for,  462 
technic  of,  463 
Lingual  duct,  25 

goiter,  85 
Lobes,  17 
Loss  of  flesh,  355 
Lymphatics,  23 


M 


M  m.h.n  w  1  goiters,  58 

clinical  aspects  of,  173 

diagnosis  of,  178 

forms  of,  80 

mechanical  symptoms  of,  126 

relation  to  surrounding  tissues,  [73 

treat  nun  t  of,  I  Ji) 
Median  goiter,  1 22 
Medicaments,  271; 
Medication,  dangers  of  iodin,  282,  41  9 

polyglandular,  427 
Mental  symptoms,  334 
Metabolism,  disturbances  in,  555 
Metastases,  65 
Metastatic  colloid  goiter,  70 
Moebtus  symptom,  j  19,  ;:| 
Muscles,  relation  of  goiter  to,  1 1 9 
Muscular  cramp,  j  j  j 
fatigue,  531,  332 
s\  mptoms  of,  j  j  1 

s\  stem,    ^41 


564 


INDEX 


Myxedema,  31,  32,  33,  182,  189,  192 

infantile,  188,  189 

operative,  182 
Myxedematous,  dystrophia,  189 

infantilism,  189 
Myxosarcoma,  79 


N 


Nanism,  188,  203,  208 

Nausea,  340 

Nerve,  hypoglossus,  129 

phrenic,  129 

spinal,  129 

sympathetic,  129 
Nerves,  lesions  of,  478 

recurrent  laryngeal,  447 

relation  of  goiter  to,  125 

vagus,  129 
Nervous  symptoms,  334 

system  in  thymectomy,  540 
vegetative,  385 
Neurasthenia,  337 
Nitrous  oxide,  498,  499 
Nodular  goiter,  57,  58,  119 

colloid,  62 
Non-toxic  vascular  goiter,  63 
Novocain,  501 
Nucleoproteid,  43 
Numbness,  346 


O 


Ocular  symptoms,  319 
Operating  room  technic,  491 
Operation,  bilateral,  454 

contra-indications  for,  299 

for  intrathoracic  goiter,  475 
indications  for,  295 
technic  of,  for  malignant  goiter,  477 

upon  thyroid  gland,  439 
unilateral,  454 
Operative  accidents,  478 
Opotherapy,  adrenalin,  428 
Crotti's  treatment,  428 
dangers  of  thyroid,  283 
in  endemic  cretinism,  289 
hypophysis,  428 

opotherapy  in  congenital  athyroid- 

ism,  288 
in  spontaneous  adult  hypothyroid- 
ism, 289 
infantile  hypothyroidism,  288 
in  surgical  athyroidism,  288 
pancreas,  428 
parathyroid,  428 
thymus,  428 
thyroid,  283 
Organic  theory,  263 
Origin  of  Graves'  disease,  nervous,  382 


Origin,  polyglandular,  388 
thyrogenetic,  372 

arguments  from  thyroid  opother- 
apy, 379 
experimental  arguments,  376 
pathological  arguments,  375 
surgical  arguments,  381 
Osseous  system,  193 
Ovarian  goiter,  87 


Pains,  345 
Palpitation,  307 
Pancreas,  390 

opotherapy,  428 
Pantopon-scopolamin,  507 
Papilloma,  74 
Paralysis,  331,  509 
Parastruma,  58,  72 
Parathyroids,  32,  392,  445 

grafting  of,  532 

number  removed  before  tetany  appears, 

529 

opotherapy,  428 

shall  we  dissect?,  458 
Parenchymatous  goiter,  57,  60,  166,  167 

diffuse,  118 
Paresis,  331 
Pathological  anatomy,  115 

planes  of  cleavage,  442 
Pathology,  57 

of  inflammation  of  thyroid,  95 

of  strumitis,  95 

of  sympathetic,  483 

of  thyroid  insufficiency,  191 

of  thyrotoxic  goiter,  315 
Pendulous  goiter,  119 
Perithelioma,  80 

Pharynx,  relation  of  goiter  to,  123 
Phosphorus  in  the  thyroid,  50 
Physiology  of  thyroid,  30 

history  of,  30 
Pigmentation,  brown,  of  skin,  348 

of  eyelids,  326 
Pleura,  injury  to,  341 
Plunging  goiter,  141,  160 
Plutonian  theory,  359 
Polydipsia,  358 
Polyglandular  medication,  427 

origin  of  Graves'  disease,  388 

treatment,  290 
Polyuria,  357 

Portion  of  thyroid  to  leave,  41 
Postbranchial  bodies,  27 

goiter,  73 
Postoperative  complications,  509 

dysphagia,  534 

fever,  523 

hematoma,  534 

hyperthyroidism,  519 


IXDEX 


565 


Postoperative  tetany,  524 
prognosis  of,  530 
symptoms  of,  524 

treatment,  493 
Pregnancy,  exophthalmic  goiter  and,  367 

simple  goiter  and,  170 
Preoperative  treatment,  489 
Proliferating  goiter,  6j 
Prophylaxis,  276 
Pulmonary  complications,  533 
Pulse,  thyrotoxic,  309 
Pyramidal  goiter,  122 

process,  18 

R 

Radiotherapy,  422 
Regulating  action,  55 
Repin's  theory,  259 
Resection,  448,  449,  452,  453 

bilateral,  456 

cuneiform,  452,  473 

enucleo-,  453 

transfrontal,  452,  473 
Respiratory  disturbances,  343 
Rest  cure,  418 
Restlessness,  334,  335,  336 
Retroesophageal  goiter,  165 
Retrotracheal  goiter,  165 


Sarcoma,  polymorphous-cell,  78 

round-cell,  78 
Sarcomata,  65 
Scar,  534 

Sensory  disturbances,  345 
Serotherapy,  426 

thyrotoxic,  427 
Sexual  apparatus,  217 
Shock,  509 

hemorrhagic,  514,  515 

psychic,  514 

toxic,  514,  515 

traumatic,  514 

treatment  of,  515 
Simple  goiter,  indications  for  operation  in, 
295 
pregnancy  and,  170 
treatment,  170 

medical,  276,  277 
Skeleton,  540 
Skin,  \<)i 

brown  pigmentation  of,  348 

itching  or,  347 

relation  of  goiter  to,  1 19 
Soda,  bicarbonate  of,  2X7 
Staring  look,  325 
Stellwag  symptom,  319,  324 
Stridor,  congenital  vestibular,  550 

Struma,  Basedow,   j  [  1 


Struma  mediana,  122 

profunda,  140 

vasculosa,  461 
Strumitis,  58,  90 

diagnosis  of,  98 

etiology  of,  93 

pathology  of,  95 

prognosis  of,  101 

symptoms  of,  95 
Suffocation,  479 
Sulphur  in  the  thyroid,  50 
Suprarenal  exhaustion,  512 
Suprarenin,  502 
Surgical  athyroidism,  196 

cachexia  strumipriva,  196 

technic,  439 
Sympathectomy,  482 

results  of,  483 

surgical  technic  for,  485 
Symptoms,  Bryson,  343 

cardiovascular,  303,  304 

Chvostek,  525 

clinical,  126 

cutaneous,  347 

Dallrymple,  319,  322 

due  to  injury  of  inferior  laryngeal  nerve, 
128 

dyspneic,  313 

Erb,  528 

eyelid,  322 

functional,  130 

Graefe,  319,  322 

Kocher,  319,  323 

mechanical,  of  malignant  goiter,  126 

mental,  334 

Moebius,  319,  324 

muscular,  331 

nervous,  334 

ocular,  319 

of  anaphylactic  origin,  402 

of  cachexia  strumipriva,  196 

of  cancer,  175 

of  circular  goiter,  163 

of  congenital  athyroidism,  207 
goiter,  167 

of  cretinism,  207 

of  infantile  hypothyroidism,  207 

of  intrathoracic  goiter,  143 

of  malignant  goiter,  175 

of  postoperative  tetany,  524 

of  spontaneous  adult   hypothyroidism, 
207 

of  strumitis,  95 

of  surgical  athyroidism,  196 

of  tetany,  524 

of  thyroiditis,  95 

of  vascular,  of  thyroid,   ]  1  j 

Stellwag,  3  [9,  324 

thyrotoxic,  of  Graves'  disease,  3^9 

I  rousseau,  526 

Vincent's  thyroideal,  105 

Weiss,  525 


566 


INDEX 


Tablets,  non-toxic  goiter,  281 
polyglandular,  428 
toxic  goiter,  428 
Tachycardia,  differential  diagnosis  of  thyro- 
toxic, 304 
etiological  explanation  of,  306 
paroxystic,  305 
Temperature,  355 
Tendinous  reflexes,  333 
Teratoma,  59,  81 
Tetany  in  animals,  33 
postoperative,  524 
in  animals,  35 
prognosis  of,  530 
symptoms  of,  524 
treatment  of,  531 
Theories  regarding  etiology  of  goiter,  241 
Thorax,  pressure  in,  546 
Thymectomy,  anesthesia  in,  557 
muscular  system  in,  541 
nervous  system  in,  540 
surgical  technic  of,  557 
with  thyroidectomy,  555 
Thymic  hyperplasia,  acute  symptoms  of,  543 
chronic  form  of,  543 
diagnosis  of,  548 

differential,  550 
relation  of,  to  Basedow's  disease, 

551 
treatment  of,  in  children    556 

complicating  Graves'  disease, 

555 
x-ray  characteristics,  550 
tracheostenosis,  542 
Thymogene-Basedow,  553 
Thymopharyngeal  duct,  537 
Thymus,  536 

Basedow  and,  552 
embryology  of,  536 
experimental  pathology  of,  540 
histology  of,  537 
hyperplasia,  474 
involution  of,  539 
opotherapy,  428 

organs  of  internal  secretion  and,  541 
pressure  of,  545,  546 
surgical  anatomy,  537 
thyroid  and,  392 
Thyrogenetic  arguments  from   thyroid  opo- 
therapy, 379 
experimental  arguments  for,  376 
origin  of  Graves'  disease,  372 
pathological  arguments  for,  375 
surgical  arguments  for,  381 
Thyroid,  action  of,  on  blood,  38 

on  cardiovascular  system,  37 

on  nervous  system,  40 

on  nutrition,  39 

on  osseous  system,  40 

of  thyroid  administration,  36 


Thyroid,  anatomical  facts  of,  440 

and  hypophysis,  55,  195,  389 

antitoxic  action  of,  53 

aplasy,  33 

arsenic  in  the,  50 

Basedow,  552 

blood  supply  of,  442 

chemistry  of,  51 

congestion  of,  114 

contusions  of,  116 

duct,  25 

elixir,  287 

function  of,  51 

gangrene  of,  98 

genital  system  and,  389 

grafting  of,  291 

hydatid  cyst  of,  113 

hypertrophy  of,  303 

inflammations  of,  89 

insufficiency  of,  191,  216 
to  prevent,  41 
treatment  of,  283 

opotherapy,  283 

dangers  of,  283 

pancreas,  adrenals,  390 

parathyroids  and,  32,  392 

phosphorus  in,  50 

physiology  of,  30 

portion  safe  to  remove,  457 

powdered  desiccated,  286 

pulsations  of,  313 

stages  of,  27 

sulphur  in,  50 

surgical  technic  of,  439 

syphilis  of,  108 

thrill  of,  313 

thymus  and,  392 

traumatic  lesions  of,  115 

tuberculosis  of,  106 

tumor  in,  130 

vascular  symptoms  of,  313 

wounds  in,  116 
Thyroidectomy,  173 

action  of,  on  metabolism,  36 

operative  technic  for,  469 

results  of  experimental,  31 

thymectomy  with,  555 
Thyroidism,  36,  285 
Thyroiditis,  58,  90 

bacterial,  90 

Basedow's  disease  and,  396 

Chagus,  1 1 1 

diagnosis  of,  98 

dissecans,  98 

etiology  of,  93 

Graves'  disease  is  a  toxic,  399,  404 

parasitic,  1 1 1 

pathology  of,  95 

pneumonic,  96 

prognosis  of,  101 

puerperal,  96 

symptoms  of,  95 


INDEX 


567 


Thyroiditis,  toxic,  103 

treatment  of,  102 

typhic,  96 

woody,  107,  109 
Thyroids,  accessory,  19 
Thyro-neuro-polyglandular  disease,  372,393, 

403 
spell,  521 
Thyroptosis,  140 
Thyrothymic  ligament,  538 
Thyrotoxic  goiter,  consistency  of,  312 
histology  of,  315 
pathology  of,  315 
surface  of,  313 
volume  of,  312 
heart,  307 
pulse,  309 
serotherapy,  427 

symptoms  of  anaphylactic  origin,  402 
tachycardia,  differential  diagnosis,  304 
etiological  explanation,  306 
Thyrotoxicosis,  303,  358,  370.     See  Graves' 

disease. 
Tingling,  346 
Trachea,  collapse  of,  479 
injury  to,  481 
relation  of  goiter  to,  120 
sabre-sheathed,  143 
I  racheotomy,  172,  481 

Transfusion,  Crotti's  technic  of  indirect,  518 
Treatment,  after-,  of  goiter  patients,  534 
Crotti's,  for  exophthalmic  goiter,  428 
for  non-toxic  parenchymatous  goi- 
ter, 281 
for  simple  goiter  and  pregnancy,  171 
ingestion  method  of,  285 
iodin,  279 
medical,  for  Graves'  disease,  405,  407, 

417 
results  of,  408 
of  cancer,  [79 
of  circular  goiter,  164 
of  congenital  goiter,  168 
of  exophthalmic  goiter  and  pregnancy, 

368 
of  (  haves'  disease,  405 

for  each  case,  434 
of  hemorrhage,  5  I  5 
of  malignant,  179 
of  shock,  515 
of  tetany,  53  I 


Treatment  of  thymic    hyperplasia   in  chil 
dren,  556 
with  Graves'  disease,  555 

of  thyroid  insufficiency,  283 

of  thyroiditis,  102 

polyglandular,  290 

postoperative,  489 

preoperative,  489 

surgical,  for  Graves'  disease,  430 
with  injections,  300 
Tremor,  303,  331 
Trousseau  symptom,  526 
Tumor  in  the  thyroid,  130 

nature  of,  132 
Tumors,  benign,  59,  60 

of  branchial  origin,  28 

connective  tissue,  59,  65,  77 

epithelial,  59,  67 

malignant,  59 

of  mesobranchial  origin,  28 

mixed,  59,  80 


U 

Urine,  modification  of,  40 
Urticaria,  348 


Vascular  goiter,  58,  63,  166 

symptoms  of  thyroid,  313 
Vasomotor  control,  loss  of,  512 

exhaustion,  509 
Wins,  imae,  20,  125 

middle,  20 

superior  thyroid,  20 
Vertigo,  346 

Vincent's  thyroidal  symptom,  105 
Vomiting,  340 


W 

Water  and  endemic  goiter,  242 

boiling  the,  289 

radioactive,  and  goiter,  262 
Weiss  symptom,  525 
When  cured,  41  s 


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